| GSE10097 |
Transcript profiling of oestrogen treatment of primary human neuronal and glial cell cultures |
The purpose of this experiment was to identify oestrogen regulated genes in human primary cell cultures of neuronal and glial cells modelling the developing human nervous system. We were especially interested in genes involved in proliferation, differentiation and migration of neuronal cells and genes involved in or linked to neurodegenerative diseases. We have therefore assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of oestrogen treated human neuronal/ glial cell cultures. We continued with 14 selected genes and confirmed the gene expression changes, by relative quantitative real time PCR, of 6 genes (p< 0.05) important in neuronal development, three of which also are suggested to have links to neurodegenerative diseases. |
GSE10097.qdab |
| GSE10691 |
Human Neuropheres |
Three week old neurospheres cultured from 18, 20 and 22 week old human fetal brain tissue, generated from epidermal growth factor, platelet-derived growth factor, and platelet-derived growth factor and neurotrophin-3. |
GSE10691.qdab |
| GSE11100 |
Dendritic Cell Vaccine against Glioblastoma Multiforme Patients |
Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. |
GSE11100.qdab |
| GSE11208 |
Chronic nicotine exposure (kuo-affy-human-232930) |
The long-term goal of this project is to establish whether and how chronic nicotine exposure affects nervous system function. The biological targets of nicotine action are diverse members of the superfamily of neurotransmitter-gated ion channels called nicotinic acetylcholine receptors (nAChR). nAChR play multiple, critical roles in chemical signaling throughout the brain and body. They also must be involved in nicotine dependence, which drives tobacco product use responsible for tremendous economic and personal costs. |
GSE11208.qdab |
| GSE11512 |
Gene expression changes during primate postnatal brain development |
In development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution. During human evolution sexual maturation has been delayed relative to other primates and this may have played a critical role for both the increase of human brain size and the rise of human-specific cognitive traits . |
GSE11512.qdab |
| GSE11882 |
Gene expression changes in the course of normal brain aging are sexually dimorphic |
This dataset of cognitively normal controls is a subset of the GSE48350 dataset, which additionally contains microarray data from AD brains. |
GSE11882.qdab |
| GSE11959 |
Anti-IGF-IR antibody h10H5 induces a unique transcriptional profile in SK-N-AS human neuroblastoma xenograft tumor |
The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through type I IGF receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-IIbinding and by inducing cell surface receptor down-regulation via internalization and degradation. In vitro, h10H5 exhibits anti-proliferative effects on cancer cell lines. In vivo, h10H5 demonstrates single-agent anti-tumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models, and even greater efficacy in combination with the chemotherapeutic agent Docetaxel or an anti-VEGF antibody. Anti-tumor activity of h10H5 is associated with decreased AKT activation and glucose uptake, and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors. |
GSE11959.qdab |
| GSE12293 |
Evolution of neuronal and endothelial transcriptomes in primates |
Neurons and endothelial cells were identified by immunohistochemistry in human brains, isolated by laser-capture-microdissection and used to find genes preferentially expressed in the two cell types. |
GSE12293.qdab |
| GSE12305 |
A 5’ Sequence of Human HMGB2 Gene for Transcriptional Targeting of Glioblastoma |
Achievement of specific tumor cell targeting remains a challenge for glioma gene therapy. We report here the identification and characterization of a 5’ sequence of human HMGB2 gene for transcriptional targeting to glioblastoma. We performed microarray analysis and found HMGB2 as one of the genes that had a low level of expression in normal human astrocytes, but was significantly up-regulated in glioblastoma cells. Real-time PCR quantification revealed increase in HMBG2 expression level in glioblastoma tissues and cells between 11 to 79 fold over that in normal human brain tissue. With progressive truncation of a 5’-upstream sequence of the HMGB2 gene, we identified a 500-bp fragment that displayed a high transcriptional activity in glioblastoma cells, but a low activity in normal brain cells. Using the sequence to drive the expression of the herpes simplex virus thymidine kinase gene in the context of a baculoviral vector, glioblastoma cells died in the presence of ganciclovir, whereas normal human astrocytes and neurons were not affected. We further confirmed that after intra-tumor injection, the baculoviral vector effectively suppressed the growth of human glioblastoma cells in a mouse xenograft model. Our results suggest that the 5’-upstream sequence of the HMGB2 gene can be used as an efficient, tumor-selective promoter in targeted vectors for glioblastoma gene therapy. |
GSE12305.qdab |
| GSE12460 |
Expression profiling of neuroblastic tumors |
The expression profiles of 64 neuroblastic tumors (mainly neuroblastoma) were determined on Affymetrix chips HG U133 Plus 2.0. |
GSE12460.qdab |
| GSE12649 |
Gene expression from human prefrontal cortex (BA46) |
Accumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ. |
GSE12649.qdab |
| GSE12685 |
Expression of mRNAs Regulating Synaptic Function and Neuroplasticity in Incipient AD |
In Alzheimer’s disease (AD), early deficits in learning and memory are a consequence of synaptic modification which are likely induced by toxic beta-amyloid oligomers (oA?). To identify molecular targets downstream of oA? binding we prepared synaptoneurosomes from frontal cortex of control and IAD patients, and isolated mRNAs for comparison of gene expression. This approach elevated synaptic mRNAs above the threshold necessary for expression changes to be discriminated and also reduced other cellular mRNAs. In patients with minimal cognitive impairment (MCI) termed incipient AD (IAD) global measures of cognition declined with increasing levels of dimeric A? (dA?). These patients also showed increased expression of neuroplasticity related genes, many encoding 3' UTR consensus sequences that regulate local translation in the synapse. One such gene, GluR2, displayed elevated mRNA and protein expression in IAD. Other neurotransmitter-related genes were also upregulated. Overexpressed genes may induce compensatory as well as negative effects on cognition and provide targets for intervention to moderate the response to dA?. |
GSE12685.qdab |
| GSE12907 |
Expression Analysis of Juvenile Pilocytic Astrocytomas by Oligonucleotide Microarray Reveals Two Potential Subgroups |
Juvenile pilocytic astrocytoma (JPA) is one of the most common brain tumors in children. The expression profiles of 21 JPAs, determined using Affymetrix GeneChip U133A, were compared with subjects with normal cerebella. The genes involved in neurogenesis, cell adhesion, synaptic transmission, central nervous system development, potassium ion transport, protein dephosphorylation, and cell differentiation were found to be significantly deregulated in JPA. These 21 JPAs were further clustered into two major groups by unsupervised hierarchical clustering using a set of 848 genes with high covariance (0.5-10). Supervised analysis with Significance Analysis of Microarrays software between these two potential subgroups identified a list of significant differentially expressed genes involved in cell adhesion, regulation of cell growth, cell motility, nerve ensheathment, and angiogenesis. Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein–positively stained tumor cells may have a higher tendency to progress. |
GSE12907.qdab |
| GSE1297 |
MMSE and NFT Test Scores for Human Alzheimer's Study |
For these data, we analyzed hippocampal gene expression of nine control and 22 AD subjects of varying severity on 31 separate microarrays. We then tested the correlation of each gene's expression with MiniMental Status Examination (MMSE) and neurofibrillary tangle (NFT) scores across all 31 subjects regardless of diagnosis. These tests revealed a major transcriptional response comprising thousands of genes significantly correlated with AD markers. Several hundred of these genes were also correlated with AD markers across only control and incipient AD subjects (MMSE > 20). |
GSE1297.qdab |
| GSE13041 |
Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age |
Background: Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear. |
GSE13041.qdab |
| GSE13141 |
Identification of candidate neuroblastoma genes by combining genomic and expression microarrays |
This SuperSeries is composed of the SubSeries listed below. |
GSE13141.qdab |
| GSE13162 |
Expression data from postmortem human brain samples with and without FTLD-U |
FTLD-U is the most common pathological correlate of the neurodegenerative dementia frontotemporal dementia |
GSE13162.qdab |
| GSE13273 |
LSD1 knock down in SY5Y Cells |
To analyze the functional relevance of LSD1 in neuroblastic tumors, SH-SY5Y cells were transiently transfected with siRNA directed against LSD1 or with a scrambled control siRNA. Microarray analysis revealed changes in expression that were consistent with these observations 72 hours after LSD1 knock-down. At this time, 28 genes were significantly induced at least 1.5-fold and 29 genes were significantly repressed at least 1.5-fold. Among the 28 induced genes, 4 are markers of cytoskeletal remodelling (TNS1, TPM1, DNM2, DNAL4), indicating differentiation, and 3 (TPM1, DNM2 and SHANK2) are functionally linked to neurite dynamics and synaptic trafficking. TaqMan quantitative RT-PCR confirmed the expression changes detected via microarray analysis for LSD1, DNAL4, DNM2, TNS1 and TPM1 |
GSE13273.qdab |
| GSE13276 |
Candidate genes for the recurrence of glioblastoma multiforme identified by microarray |
Background: Glioblastoma multiforme (GBM) is the most aggressive and most lethal primary malignant brain tumor, correlated with survival rates of less than one year from the time of diagnosis. Current surgical procedure attempts to remove the bulk of the tumor mass, whereas GBM frequently recurs within 1-3cm from the primary tumor resection site. Molecular mechanisms involved in the recurrence of the tumor are still poorly understood. The aim of the study was to define the molecular signature of GBM surrounding white matter (WM) in order to better understand the molecular mechanisms involved with tumor relapse. |
GSE13276.qdab |
| GSE13307 |
Microarray analysis of neural progenitor cells (hNPC) derived from the developing cortex (CTX) and ventral midbrain (VM) |
Neural progenitor cells (hNPC) derived from the developing human brain can be expanded in culture and subsequently differentiated into neurons and glia. They provide an interesting source of tissue for both modeling brain development and future cellular replacement therapies. It is becoming clear that hNPC are regionally and temporally specified depending on which brain region they were isolated from and its developmental stage. We show here that hNPC derived from the developing cortex (hNPCCTX) and ventral midbrain (hNPCVM) have similar morphological characteristics and express the progenitor cell marker nestin. However, hNPCCTX cultures were highly proliferative and produced large numbers of neurons, while hNPCVM divided slowly and produced less neurons but more astrocytes. Microarray analysis revealed a similar expression pattern for some stemness markers between the two growing cultures, overlaid with a regionally specific profile that identified some important differentially expressed neurogenic transcription factors. By over expressing one of these, the transcription factor ASCL1, we were able to regain neurogenesis from hNPCVM cultures which produced larger neurons with more neurites than hNPCCTX, but no fully mature dopamine neurons. Thus hNPC are regionally specified and can be induced to undergo neurogenesis following genetic manipulation. While this restores neuronal production with a region specific phenotype, it does not restore full neurochemical maturation which may require additional factors. |
GSE13307.qdab |
| GSE13564 |
Gene expression in the human prefrontal cortex during postnatal development |
Fresh frozen post mortem prefrontal cortex tissue (Brodman area 46) was obtained from 44 individuals varying in age from 0 to 49 years. RNA was extracted from these samples and hybridized to HG133plus2.0 GeneChips. The data was used to examine patterns of gene expression over the course of human postnatal developmental and ageing. |
GSE13564.qdab |
| GSE13715 |
Expression data from Neural Progenitor cells cultured on 2D flat surfaces and in 3D scaffolds |
A genomic expression comparison was done among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neural spheres (in vivo surrogate), with the goal of assessing the feasibility of establishing the meaning of 3D and associated physiological relevance at the molecular level |
GSE13715.qdab |
| GSE14038 |
Integrative genomic analyses of neurofibromatosis tumors identify SOX9 as biomarker and survival gene |
Understanding biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumors is essential, as tumor biomarkers, prognostic factors and therapeutics are all lacking. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (n = 22), malignant peripheral nerve sheath tumor (MPNST) cell lines (n = 13), benign neurofibromas (n = 26) and MPNST (n = 6). Dermal and plexiform neurofibromas were indistinguishable. A prominent theme in the analysis was aberrant differentiation. Neurofibromas repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes upregulated in the sarcomas were significantly enriched for genes activated in neural crest cells. We validated differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in neurofibroma and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumors - caused MPNST cell death. SOX9 is a biomarker of neurofibroma and MPNST, and possibly a therapeutic target in NF1. |
GSE14038.qdab |
| GSE14098 |
Gene expression profiles obtained from laser-microdissected human choroid plexus papilloma cells |
Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. |
GSE14098.qdab |
| GSE14108 |
Brain metastasis from lung adenocarcinoma patients |
Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients. |
GSE14108.qdab |
| GSE14340 |
Transcriptional profiling of human neural crest cells |
The expression profiles of five human trunk level neural crest cell lines were determined on Affymetrix chips HG U133 Plus 2.0. |
GSE14340.qdab |
| GSE14880 |
Differentation in neuroblastomas |
Expression profiling according to differentiation was analysed in 34 neuroblastomas |
GSE14880.qdab |
| GSE15163 |
Gene expression data from primate postnatal brain development - superior frontal gyrus |
In development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution. During human evolution sexual maturation has been delayed relative to other primates and this may have played a critical role for both the increase of human brain size and the rise of human-specific cognitive traits . |
GSE15163.qdab |
| GSE15209 |
Expression data from human foetal neural stem (NS) cell lines and human glioma neural stem (GNS) cell lines |
Gliomas have been proposed to be driven by a population of neural stem-like cells. We isolated a panel of novel human glioma cell lines using adherent neural stem cell conditions. |
GSE15209.qdab |
| GSE15583 |
Neuroblastoma cell lines under normoxic and hypoxic conditions |
Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. |
GSE15583.qdab |
| GSE15757 |
PRC2 in Ewing tumors |
We found the PRC2 component EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in Ewing tumors and mesenchymal stem cells (Richter GH et al., Proc Natl Acad Sci U S A. 2009;106:5324-9). Downregulation of EZH2 by RNA interference in Ewing tumor cell lines suppressed oncogenic transformation in vitro and in vivo. These data suggest that EZH2 might play a central role in Ewing Tumor pathology. |
GSE15757.qdab |
| GSE15824 |
Gene expression profiling of human gliomas and human glioblastoma cell lines |
To identify signaling pathways that are differentially regulated in human gliomas, a microarray analysis on 30 brain tumor samples (12 primary glioblastomas (GBM), 3 secondary glioblastomas (GBM-2), 8 astrocytomas (Astro) and 7 oligodendrogliomas (Oligo)) and on 5 glioblastoma cell lines (LN018, LN215, LN229, LN319 and BS149) was performed. Normal brain tissue (NB) and normal human astrocytes (NHA) were used as a control. Kinase expression in each tumor was compared to expression in normal brain and expression values from normal human astrocytes were used as an additional control. |
GSE15824.qdab |
| GSE16119 |
GBM and microglia fraction of same glioblastoma multiforme (GBM) |
Little is known about the immune performance and interactions of CNS microglia/macrophages in glioma patients. Microglia/macrophages were found to be the predominant immune cell infiltrating gliomas (approximately 1% of total cells); others identified are myeloid dendritic cells (DCs), plasmacytoid DCs, and T cells. Using a procedure enriching for CD11b/c+CD45+ glioma-infiltrating microglia/macrophages (GIMs) from postoperative tissue specimens of glioma patients (Hussain et al. Neuro Oncol. 2006 J;8(3):261-79) gene expression profiles were obtained form paired samples. The expression profiles are used to identify expression signatures contributed by GIMs in glioblastoma data sets (Murat et al, submitted). |
GSE16119.qdab |
| GSE16155 |
Expression data from ependymoma surgical samples |
Ependymoma, the 3rd most common brain tumor in children, recurs in approximately 50% of patients. There is currently no robust marker that predicts for recurrence, which is a significant clinical problem |
GSE16155.qdab |
| GSE16237 |
Expression data of human neuroblastoma tissue samples |
The prognosis of the patients with neuroblastoma largely depends on the biological characterisitics. Neuroblastoma tissues obtained before any treatments were analyzed for gene expression using Affymetrix array. |
GSE16237.qdab |
| GSE16450 |
Human BE(2)-C neuronal responses to type I IFN stimulation |
Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections. |
GSE16450.qdab |
| GSE16451 |
Human BE(2)-C neuronal responses to WEEV infection |
Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections. |
GSE16451.qdab |
| GSE16476 |
Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma |
mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF? pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. |
GSE16476.qdab |
| GSE16581 |
Genomic landscape of meningiomas: gene expression |
Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed global genetic and genomic analysis of 85 meningioma samples of various grades. |
GSE16581.qdab |
| GSE16656 |
Transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblatoma SH-SY5Y cells: 24h |
The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces ER stress response as major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE. |
GSE16656.qdab |
| GSE16759 |
mRNA and miRNA expression in parietal lobe cortex in Alzheimer's disease |
In this study, we jointly profiled mRNA and miRNA expression to determine the role of miRNAs in AD, and whether the levels of miRNAs are related to those of target mRNAs. We found a bias towards positive correlation between levels of miRNAs and those of their targets. |
GSE16759.qdab |
| GSE16766 |
Transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells: 1h |
The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE. |
GSE16766.qdab |
| GSE16767 |
Transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells: 4h |
The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE. |
GSE16767.qdab |
| GSE16969 |
Gene expression analysis of TSC-tubers reveals increased expression of adhesion and inflammatory factors |
Cortical tubers in patients with tuberous sclerosis complex (TSC) are associated with cognitive disability and intractable epilepsy. While these developmental malformations are believed to result from the effects of TSC1 or TSC2 Gene mutations, the molecular mechanisms leading to tuber formation during brain development as well as the onset of seizures remain largely unknown. We used the Affymetrix Gene Chip platform as a genome-wide strategy to define the Gene expression profile of cortical tubers resected during epilepsy surgery compared to histologically normal perituberal tissue (adjacent to the cortical tuber) from the same patients or autopsy control tissue. |
GSE16969.qdab |
| GSE17204 |
Parkinson's disease-associated DJ-1 is required for the expression of GDNF receptor Ret in human neuroblastoma cells |
DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinson’s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration. |
GSE17204.qdab |
| GSE17491 |
Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-Infected Brain |
This SuperSeries is composed of the SubSeries listed below. |
GSE17491.qdab |
| GSE17612 |
Comparison of post-mortem tissue from brain BA10 region between schizophrenic and control patients. |
Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. |
GSE17612.qdab |
| GSE17645 |
Transcript profiling of oestrogen treatment of primary human neuronal cell cultures |
The purpose of this experiment was to identify oestrogen regulated genes in human primary cell cultures of neuronal cells modelling the developing human nervous system. We were especially interested in genes involved in proliferation, differentiation and migration of neuronal cells and genes involved in or linked to neurodegenerative diseases. We have therefore assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of oestrogen treated human neuronal cell cultures. |
GSE17645.qdab |
| GSE17714 |
11 Neuroblastoma cell lines under normoxic and hypoxic conditions |
Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. |
GSE17714.qdab |
| GSE18015 |
Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas. |
Background: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. |
GSE18015.qdab |
| GSE18144 |
Array-based gene expression, CGH and tissue data define a 12q24 gain in neuroblastic tumors with prognostic implication |
This SuperSeries is composed of the SubSeries listed below. |
GSE18144.qdab |
| GSE1825 |
SRBCT |
Comparison of gene expression profiles between neuroblastoma samples and Ewing family tumor samples. RNA from native tumor samples was processed for DNA-microarray analysis using Affymetrix HG-U133A microarrays. Primary image analysis was performed using MAS 5.0 and data were scaled to an target intesity of 500. |
GSE1825.qdab |
| GSE18271 |
Analysis of TALE homeobox genes in neuroblastic tumors: ganglioneuroblastoma and ganglioneuroma |
A large proportion of patients suffering from the malignant pediatric tumor neuroblastoma die of progressive disease despite intensive therapy. Neuroblastomas belong to the group of neuroblastic tumors, together with the more benign, differentiated ganglioneuroblastomas and ganglioneuromas. Little is known of the genes driving the differentiation processes in these tumor types. A search for the transcription factors differentially expressed between ganglioneuromas, ganglioneuroblastomas, and neuroblastomas in a series of 110 neuroblastic tumors (NB110) identified a large number of HOX- and TALE (Three Amino acid Loop Extension)-class homeobox transcription factor genes. The MEIS1-3, PBX1 and -3, and PKNOX1 TALE genes showed highest expression in neuroblastomas and lowest in ganglioneuromas and ganglioneuroblastomas. The PKNOX2 and TGIF1-2 genes showed the opposite expression pattern. This suggests an involvement of TALE genes in neuroblastoma differentiation. Expression of MEIS1, a known oncogene in haematopoietic tumors, was high in all neuroblastomas, and strongly correlated with undifferentiated histology. Consequently, we generated IMR-32 neuroblastoma cells capable of inducible shRNA-mediated MEIS1 knockdown. We observed differentiation, growth arrest and induction of apoptosis upon MEIS1 down-regulation. Affymetrix profiling of time-course experiments using these cells allowed the identification of MEIS1 target genes. Analysis of the target genes in the NB110 series showed that 323 of these were also significantly correlated to MEIS1 expression and to tumor differentiation in neuroblastic tumors. Genes involved in the cell cycle and in developmental pathways were over-represented in this gene set. We conclude that MEIS1 governs several of the signal transduction routes important for neuroblastoma survival and differentiation. |
GSE18271.qdab |
| GSE18296 |
Gene Expression Profiling of an Immortalized Human Neural Stem Cell Line HB1.F3 |
Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat spinal cord injury, stroke, and neurodegenerative diseases. To efficiently induce neuronal lineage cells from NSC for neuron replacement therapy, we should clarify the intrinsic genetic programs involved in a time and place-specific regulation of human NSC differentiation. Recently, we established an immortalized human NSC clone HB1.F3 to provide an unlimited NSC source applicable to genetic manipulation for cell-based therapy. To investigate a role of neurogenin 1 (Ngn1), a proneural basic helix-loop-helix (bHLH) transcription factor, in human NSC differentiation, we established a clone derived from F3 stably overexpressing Ngn1. Genome-wide gene expression profiling identified 250 upregulated genes and 338 downregulated genes in Ngn1-overexpressing F3 cells (F3-Ngn1) versus wild-type F3 cells (F3-WT). Notably, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a novel stem cell marker, showed a robust increase in F3-Ngn1. |
GSE18296.qdab |
| GSE18349 |
Expression data from +7 hNPCs and diploid hNPCs |
Human Neural progenitor cells have been found to have karyotypic abnormalities. In this study we explored the gene changes between hNPCs that are karyotypically normal and hNPCs with a trisomy of chromosome 7. |
GSE18349.qdab |
| GSE18409 |
Expression data from Trk-overexpressing NB cell line SY5Y |
Neurotrophin receptors play a pivotal role in the biology and prognosis of neuroblastoma (NB). While expression of TrkA/NTRK1 confers a good prognosis to NB patients, expression of TrkB/NTRK2 is associated with unfavorable outcome. We have transfected the neurotrophin-receptor null cell line SY5Y with either full-length TrkA or TrkB and performed transcriptional profiling to analyse the effects of Trk-expression without activation and in a time course after activation. |
GSE18409.qdab |
| GSE18632 |
Knockdown of transactive response DNA-binding protein TDP-43 downregulates histone deacetylase 6 |
TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43 silenced cells. This was completely restored by co-transfection with HDAC6. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis. |
GSE18632.qdab |
| GSE18696 |
Comparison of human lower and upper entorhinal cortex layers gene expression |
Specific vulnerability of neurons in the human entorhinal cortex has been associated with the onset of disease. |
GSE18696.qdab |
| GSE18959 |
Comparison of neuroepithelial cells and regionally specified astrocytes from human embryonic stem cells |
These arrays were conducted in order to confirm the generation of astrocytes from human embryonic stem cells and to determine expression differences between astrocyte subtypes. |
GSE18959.qdab |
| GSE1923 |
Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells |
Overall study: Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells. |
GSE1923.qdab |
| GSE19332 |
Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS) |
Gene expression profiling has been performed on motor cortex and spinal cord homogenates and of sporadic ALS cases and controls, to identify genes and pathways differentially expressed in ALS. More recent studies have combined the use of laser capture microdissection (LCM) with gene expression profiling to isolate the motor neurons from the surrounding cells, such as microglia and astrocytes, in order to determine those genes differentially expressed in the vulnerable cell population – i.e. motor neuron. |
GSE19332.qdab |
| GSE19345 |
Human Cytomegalovirus Infection Causes Premature and Abnormal Differentiation of Human Neural Progenitor Cells |
Our results suggest that HCMV infection disrupts the self-renewal capacity of NPCs and influences their differentiation. |
GSE19345.qdab |
| GSE19350 |
Array-based bioinformatic analysis on pediatric primary central nervous system germ cell tumors |
This SuperSeries is composed of the SubSeries listed below. |
GSE19350.qdab |
| GSE19404 |
Gene expression analysis of primitive neuroectodermal tumors |
Central nervous system primitive neuroectodermal tumors (CNS PNET) and medulloblastomas are both embryonal tumors that predominantly occur in children. |
GSE19404.qdab |
| GSE20141 |
Expression analysis of laser-dissected SNpc neurons in Parkinson's disease |
Genome-wide transcriptome analysis of expression changes in laser-dissected SNpc neurons from Parkinson's disease brain tissue versus control brain tissue. |
GSE20141.qdab |
| GSE20146 |
Expression analysis of dissected GPi in Parkinson's disease |
Genome-wide transcriptome analysis of expression changes in Globus Pallidus interna (GPi) from Parkinson's disease brain tissue versus control brain tissue. |
GSE20146.qdab |
| GSE20163 |
Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 2 |
Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. |
GSE20163.qdab |
| GSE20164 |
Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 3 |
Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. |
GSE20164.qdab |
| GSE20314 |
Systematic meta-analysis and replication of genome-wide expression studies of Parkinson’s disease: 4 |
Analysis of substantia nigra from postmortem brains of 4 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. |
GSE20314.qdab |
| GSE20333 |
Gene expression profiling of parkinsonian substantia nigra |
Affymetrix HG-Focus array was used to determine a global gene expression profile of clinically and neuropathologically confirmed cases of sporadic Parkinson's disease compared to controls. |
GSE20333.qdab |
| GSE20589 |
Microarray analysis identifies the gene signature of surviving motor neurons in human SOD1-related motor neuron disease |
Gene expression profiling has been performed previously on motor cortex and spinal cord homogenates and of sporadic ALS cases and controls, to identify genes and pathways differentially expressed in ALS. More recent studies have combined the use of laser capture microdissection (LCM) with gene expression profiling to isolate the motor neurons from the surrounding cells, such as microglia and astrocytes, in order to determine those genes differentially expressed in the vulnerable cell population – i.e. motor neuron. |
GSE20589.qdab |
| GSE20736 |
Microarray analysis of differentiation of human glioblastoma stem cells |
Glioblastoma multiforme is one of the most devastating cancers and presents unique challenges to therapy due to its aggressive behaviour. Cancer stem cells have been described to be the only cell population with tumorogenic capacity in glioblastoma. Therefore, effective therapeutic strategies targeting these cells may be beneficial. We have established different cultures of glioblastoma stem cells (GSCs) derived from surgical specimens and found that, after induction of differentiation, NF?B was activated, which allows intermediate tumor precursor cells to remain cycling. We also showed that blockade of NF?B signaling in differentiating GSCs by different genetic strategies or treatment with small molecule inhibitors, promoted replication arrest, progression to a mature phenotype, mainly neuronal cells, and senescence. This effect was partly mediated by downregulation of the NF?B target gene cyclin D1. Furthermore, intravenous treatment of immunodeficient mice bearing human GSC-derived tumors with a novel small-molecule inhibitor of the NF?B pathway induced senescence of tumor cells but no ultraestructural alterations of the brain parenchymal cells were detected. These findings reveal that activation of NF?B may keep differentiating GSCs from acquiring a mature postmitotic phenotype, thus allowing cell proliferation, and support the rationale for therapeutic strategies aimed at promoting premature senescence in GSCs undergoing differentiation. |
GSE20736.qdab |
| GSE21298 |
Profiling wt SOD versus ALS SOD1(G93A) mutant |
Whole-genome profiling of SH-SY5Y cells was done on neuroblastoma SH-SY5Y stably transfected with cDNAs coding for SOD1WT or the mutant SOD1(G93A) protein. |
GSE21298.qdab |
| GSE21305 |
Profiling neuroblastoma SH-SY5Y with Paraquat treatment |
Human SH-SY5Y neuroblastoma cells treated with paraquat, a neurotoxic herbicide which both catalyzes the formation of reactive oxygen species (ROS) and induces mitochondrial damage in animal models was profiled using Affimetrix Exon 1.0 ST GeneChips® |
GSE21305.qdab |
| GSE21336 |
GBM_SC_retinoic acid_gene_expression |
This study compared the gene expression change of glioblastoma stem-like cells before and after retinoic acid treatment |
GSE21336.qdab |
| GSE21570 |
Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial in vivo intracranial transplantation |
One of the most detrimental hallmarks of glioblastoma multiforme (GBM) is cellular invasiveness, considered a potential cause of tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding the various mechanisms controlling GBM invasiveness, the nature of the invasiveness remains poorly characterized. Here, we established a highly invasive glioma cell line (U87MGR2/R3 cells) and a non-invasive cell line (U87MGL2/L3 cells) from U87MG glioma cells following four rounds of serial in vivo intracranial transplantation. Compared to U87MGL2/L3 cells, U87MGR2/R3 cells were highly invasive and had glioma stem cell-like properties. Microarray analysis showed that apoptosis-inducing genes (caspase3 and PDCD4) were downregulated, whereas several cancer stem cell-relevant genes (Wnt10A, Frizzled 4, and CD44) were upregulated in U87MGR2/R3 cells compared to U87MGL2/L3 cells. U87MGR2/R3 cells were resistant to anticancer drug-induced cell death, which was partially due to downregulation of caspase3 and PDCD4. U87MGR2/R3 cells retained activated Wnt/?-catenin signaling through Frizzled 4, which was sufficient to control neurosphere formation. In addition, Frizzled 4 promoted expression of the epithelial to mesenchymal transition regulator, SNAI1, and acquisition of a mesenchymal phenotype. Taken together, our results indicate that Frizzled 4 may be a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and may be a major cause of GBM recurrence and poor prognosis. |
GSE21570.qdab |
| GSE2164 |
Summary T-test |
Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences. |
GSE2164.qdab |
| GSE21713 |
mRNA expression data from primary untreated neuroblastoma tumour samples |
The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells. |
GSE21713.qdab |
| GSE21779 |
Gene expression data from temporal cortex of young adult, old and AD-like Microcebus murinus |
Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented b-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in “AD-like” animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in “AD-like” animals. These results open the way to new exploration of physiological and “AD-like” aging in primates. |
GSE21779.qdab |
| GSE21858 |
Patterns of gene expression and evolution in the human developing cerebral cortex |
The cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown. |
GSE21858.qdab |
| GSE21935 |
Comparison of post-mortem tissue from Brodman Brain BA22 region between schizophrenic and control patients |
Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development |
GSE21935.qdab |
| GSE22467 |
Impact of NRSF variant over-expression in SK-N-AS human neuroblastoma cells |
Neuron-restrictive silencer factor (NRSF) and its isoforms are differentially regulated in rodent models of self-sustaining status epilepticus (SSSE). NRSF isoforms regulate genes associated with SSSE, including the proconvulsant tachykinins, brain-derived neurotrophic factor and multiple ion channels. NRSF isoforms may direct distinct gene expression patterns during SSSE and the ratio of each isoform may be a causative factor in traumatic damage to the CNS. Here we analysed global gene expression changes by microarray in human SK-N-AS neuroblastoma cells following the over expression of NRSF and a truncated isoform, HZ4. |
GSE22467.qdab |
| GSE22521 |
Gene expression in primate postnatal brain through lifespan - prefrontal cortex |
We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities. |
GSE22521.qdab |
| GSE22569 |
Gene expression in primate postnatal brain through lifespan - cerebellar cortex |
We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities. |
GSE22569.qdab |
| GSE22771 |
Anaplastic lymphoma kinase (ALK) inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels. |
High anaplastic lymphoma kinase (ALK) protein levels may be correlated with an unfavorable prognosis in neuroblastoma (NBL) patients, regardless of ALK mutation status. We therefore examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated (MUT) and wild type (WT) NBL cell lines. Six of the nineteen NBL cell lines had a point mutation and four an amplification of the ALK gene. ALK amplified cell lines showed similar ALK levels and ALK inhibitor sensitivity as WT cell lines and were therefore co-analyzed. The ALK mRNA (p=0.043), ALK 220 kDa (p=0.009) and ALK 140 kDa (p=0.025) protein levels were higher in ALK mutant (n=6) than WT cell lines (n=13). ALK mRNA and protein levels significantly correlated with ERK1 and ERK2 protein levels, and also with PHOX2B mRNA levels, a neural differentiation marker which is mutated in NBL. Response to ALK inhibitor TAE684 was also significantly correlated with ALK levels. ALK mutant cell lines (n=4) demonstrated a higher sensitivity towards ALK inhibitor TAE684 (14.9 fold more sensitive, p=0.004) than eight WT cell lines. These results underline the importance of ALK mutations but also ALK levels for response to ALK inhibitors in NBL cell lines. Furthermore, the strong correlation of PHOX2B and ALK suggests that neural differentiation stage may be correlated with ALK levels in neuroblastoma. These data will enhance understanding of ALK inhibitor response in future patient trials. |
GSE22771.qdab |
| GSE22772 |
Expression data from U373 cells expressing EGFP, MAML1-dn and DTX1-myc |
Glioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJ?-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKB? and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases. |
GSE22772.qdab |
| GSE22927 |
Hierarchical synergy of Pten, p53 and Rb pathways in high-grade astrocytoma induced in adult brain |
Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain. |
GSE22927.qdab |
| GSE23290 |
Microarray expression analysis in idiopathic and LRRK2-associated Parkinson's disease |
LRRK2 mutations are the most common genetic cause of Parkinson’s disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment. |
GSE23290.qdab |
| GSE23579 |
Gene expression profilings of fetal human and mouse cerebral cortex exposed to alcohol |
A dataset for coordinated transcriptome analysis of the effect of ethanol on human embryonic cerebral slices in vitro and on the mouse embryonic cerebral cortex in a in vivo model. |
GSE23579.qdab |
| GSE2378 |
Normal and glaucomatous astrocytes |
Astrocytes from optic nerve head from donors with and without glaucoma |
GSE2378.qdab |
| GSE2393 |
Expression patterns throughout disease progression and impact on neuroAIDS. |
The virus/host interactions during the acute phase of human immunodeficiency virus (HIV) infection help determine the course of disease. During this time period, virus enters the brain. Here, we report clusters of genes whose transcripts are significantly upregulated in the frontal lobe of the brain during acute simian immunodeficiency virus (SIV) infection of rhesus monkeys. Many of these genes are involved in interferon (IFN) and/or interleukin (IL)-6 pathways. Although neither IFNa nor IFN? are elevated in the brain, IL6 is increased. Both IFNa and IL6 are elevated in plasma during this acute phase. The upregulation of STAT1, verified by immunohistochemical staining, can be due to both central nervous system (CNS) (SIV and IL6) and peripheral (IFNa and IL6) causes, and can itself drive the expression of many of these genes. Examination of the levels of expression of the upregulated genes in the post-acute and long-term phases of infection, as well as in SIV encephalitis, reveals increased expression throughout SIV infection, which may serve to protect the brain, but can have untoward long-term consequences. |
GSE2393.qdab |
| GSE24244 |
Gene expression profiling of four subpopulations in GBM |
GBM is a heterogenous brain tumor with hyperproliferation of endothelial cells. In order to understand the cellular mechanism of vasculogenesis in GBM, four fractions of cells are seperated. Microarray assays was performed to examine the potential lineage relationship and the signal pathways involved in determining the cell identity and function. |
GSE24244.qdab |
| GSE24265 |
Expression data from human brain samples |
Spontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. |
GSE24265.qdab |
| GSE24378 |
Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease |
Analysis of human dopamine (DA) from postmortem brains of 8 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. |
GSE24378.qdab |
| GSE24557 |
Exon-level expression profiles of GBM brain tumors |
Transcriptome analysis of RNAs from brain tumor |
GSE24557.qdab |
| GSE24558 |
GBM brain tumors |
This SuperSeries is composed of the SubSeries listed below. |
GSE24558.qdab |
| GSE25012 |
WNT pathway activation promotes phenotypic reprogramming of glioblastoma derived cells in zebrafish nervous system microenvironment |
phenotypic reprogramming ability of teh zebtafish brain microenviroment on GBM derived cells controlled by the activation of endogenous Wnt pathway |
GSE25012.qdab |
| GSE25496 |
Transcriptome analysis of the Nasu-Hakola disease brain |
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; OMIM 221770), is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DAP12 and TREM2, which constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells, macrophages, and microglia. No Japanese patients with TREM2 mutations have been reported previously. We reported three siblings affected with NHD in a Japanese family. Among them, two died of NHD during the fourth decade of life. The transcriptome was studied in the autopsized brain of one patient. We found a homozygous conversion of a single nucleotide T to C at the second position of intron 3 in the splice-donor consensus site (c.482+2T>C) of the TREM2 gene, resulting in exon 3 skipping. We identified 136 upregulated genes involved in inflammatory response and immune cell trafficking and 188 downregulated genes including a battery of GABA receptor subunits and synaptic proteins in the patient’s brain. |
GSE25496.qdab |
| GSE25673 |
Comparing Control and Schizophrenic hiPSC-derived Neurons |
Schizophrenia is a debilitating neurological disorder for which no cure exists. Few defining characteristics of schizophrenic neurons have been identified and the molecular mechanisms responsible for schizophrenia are not well understood, in part due to the lack of patient material for study. Human induced pluripotent stem cells (hiPSCs) offer a new strategy for studying schizophrenia. We have created the first cell-based human model of a complex genetic psychiatric disease by generating hiPSCs from schizophrenic patients and subsequently differentiating these cells to hiPSC-derived neurons in vitro. Schizophrenic hiPSC-derived neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of schizophrenic hiPSC-derived neurons identified altered expression of many components of the cAMP and WNT signaling pathways. Key cellular and molecular elements of the schizophrenic phenotype were ameliorated following treatment of schizophrenic hiPSC-derived neurons with the antipsychotic loxapine. |
GSE25673.qdab |
| GSE26458 |
Effects of IKAP/hELP1 deficiency on gene expression in differentiating neuroblastoma cells, implications for Familial dysautonomia |
Investigate IKAP importance in the development of neuronal cells, in order to understand Familial dysautonomia phenotype. |
GSE26458.qdab |
| GSE26535 |
Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation. |
OBJECTIVE: Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self-renewal and fate. |
GSE26535.qdab |
| GSE26545 |
MicroRNA expression and regulation in human, chimpanzee, and macaque brain |
Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence between adult humans, chimpanzees and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using combination of high-throughput sequencing, miRNA microarrays and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% - between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2-4% of mRNA and 4-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, were further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions. |
GSE26545.qdab |
| GSE26586 |
Widespread splicing changes in human brain development and aging |
Differences in transcript splicing are well documented among tissues and between sexes in humans and other organisms. Further, splicing changes in selected genes have been reported in human and mouse brain development. Using high-throughput RNA sequencing we characterized the transcriptome-wide splicing changes occurring over the lifespan in the human brain. We found that in two brain regions, prefrontal cortex and cerebellum, as many as 37% of all expressed protein-coding multi-exon genes undergo significant splicing changes between birth and 98 years of age. Approximately 40% of these changes take place in aging. We confirmed our findings using exon arrays and PCRs and detected identified splicing changes at the protein level. We further associated distinct patterns of age-related splicing changes with expression of the corresponding splicing factors. Thus, splicing plays an important role in shaping the human brain transcriptome in both development and aging. |
GSE26586.qdab |
| GSE26629 |
Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells: proof of principle and preliminary findings |
Induced pluripotent stem cell (iPSC) technology has the potential to address the inaccessibility of the human brain by providing investigators with patient-specific neurons that can potentially be used to carry out molecular, electrophysiological and pharmacological studies {{855 Takahashi,K. 2006}}. Although iPSC technology was primarily conceived and developed as a means to bypass the use of human embryonic stem cells (hESCs) for regenerative medicine, its potential for disease modeling may prove to be equally valuable, especially for neuropsychiatric disorders. |
GSE26629.qdab |
| GSE27505 |
Prospective Identification, Isolation, and Profiling of a Telomerase-Expressing Subpopulation of Human Neural Stem Cells, using sox2 Enhancer-Directed Fluorescence-Activated Cell Sorting |
Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors. |
GSE27505.qdab |
| GSE27667 |
Gene expression of induced neural stem cells |
Neural stem cell (NSC) transplantation replaces damaged brain cells and provides disease-modifying effects in many neurological disorders. However, there has been no efficient way to obtain autologous NSCs in patients. Given that ectopic factors can reprogram somatic cells to be pluripotent, we attempted to generate human NSC-like cells by reprograming human fibroblasts. Fibroblasts were transfected with NSC line-derived cellular extracts and grown in neurosphere culture conditions. The cells were then analyzed for NSC characteristics, including neurosphere formation, gene expression patterns, and ability to differentiate. The obtained induced neurosphere-like cells (iNS), which formed daughter neurospheres after serial passaging, expressed neural stem cell markers, and had demethylated SOX2 regulatory regions, all characteristics of human NSCs. The iNS had gene expression patterns that were a combination of the patterns of NSCs and fibroblasts, but they could be differentiated to express neuroglial markers and neuronal sodium channels. These results show for the first time that iNS can be directly generated from human fibroblasts. Further studies on their application in neurological diseases are warranted. |
GSE27667.qdab |
| GSE27931 |
An RNAi Screen Identifies TRRAP as a Regulator of Brain Tumor-Initiating Cell Differentiation |
Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor. The brain-infiltrative character of glioblastoma makes complete surgical removal of the tumor impossible and neither radiation nor current chemotherapy provide cure. Recent evidence shows that glioblastoma multiforme consists of heterogeneous cell populations which differ in tumor-forming potential. Enriched tumor-initiating capacity has been linked to poorly differentiated glioblastoma cells sharing features with neural stem cells. Thus, these cells are important targets for new therapeutic strategies. |
GSE27931.qdab |
| GSE28019 |
Neuroblastoma cell line profiling |
24 standard human Neuroblastoma Cell lines were profiled without applying any transfections in order to measure the expression profiles. |
GSE28019.qdab |
| GSE28146 |
Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer’s disease |
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that threatens to reach epidemic proportions as our population ages. Although much research has examined molecular pathways associated with AD, relatively few studies have focused on critical early stages. Our prior microarray study correlated gene expression in human hippocampus with AD markers. Results suggested a new model of early-stage AD in which pathology spreads along myelinated axons, orchestrated by upregulated transcription and epigenetic factors related to growth and tumor suppression (Blalock et al., 2004). However, the microarray analyses were performed on RNA from fresh frozen hippocampal tissue blocks containing both gray and white matter, potentially obscuring region-specific changes. In the present study, we used laser capture microdissection to exclude major white matter tracts and selectively collect CA1 hippocampal gray matter from formalin-fixed, paraffin-embedded (FFPE) hippoc ampal sections of the same subjects assessed in our prior study. Microarray analyses of this gray matter-enriched tissue revealed many correlations similar to those seen in our prior study, particularly for neuron-related genes. Nonetheless, in the laser-captured tissue, we found a striking paucity of the AD-associated epigenetic and transcription factor genes that had been strongly overrepresented in the prior tissue block study. In addition, we identified novel pathway alterations that may have considerable mechanistic implications, including downregulation of genes stabilizing ryanodine receptor Ca2+ release and upregulation of vascular development genes. We conclude that FFPE tissue can be a reliable resource for microarray studies, that upregulation of growth-related epigenetic/ transcription factors with incipient AD is predominantly localized to white matter, further supporting our prior findings and model, and that alterations in vascular and ryanodine receptor-relat ed pathways in gray matter are closely associated with incipient AD. |
GSE28146.qdab |
| GSE28160 |
Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders |
Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. |
GSE28160.qdab |
| GSE2817 |
Wavelet modelling of microarray data provides chromosomal pattern of expression which predicts survival in gliomas |
Genetic and epigenetic processes result in gene expression changes through alteration of the chromatin structure. The relative position of genes on chromosomes has therefore important functional implications and can be exploited to model microarray datasets. Gliomas are the most frequent primary brain tumours in adults and their prognosis is related to histology and grade. In oligodendrogliomas, allelic loss of 1p/19q and hypermethylation of MGMT promoter is associated with longer survival and chemosensitivity. In this work we used oligonucleotide microarray to study a group of 30 gliomas with various oligodendroglial and astrocytic components. We used an original approach combining a wavelet model of inter-probe genomic distance (CHROMOWAVE) and unsupervised method of analysis (Singular Value Decomposition) in order to discover new prognostic chromosomal patterns of gene expression. We identified a major pattern of variation that strongly correlated with survival (p= 0.007) and could be visualized as a genome-wide chromosomal pattern including widespread gene expression changes on 1p, 19q, 4, 18, 13 and 9q and multiple smaller clusters scattered along chromosomes. Gene expression changes on chromosomes 1p, 19q and 9q were significantly correlated with the allelic loss of these regions as measured by FISH. Differential expression of genes implicated in drug resistance was also a feature of this chromosomal pattern and in particular low expression of MGMT was correlated with favourable prognosis (p<0.0001). Remarkably, unsupervised analysis of the expression of individual genes and not of their chromosomal ensemble produced a pattern that could not be associated with prognosis, emphasizing the determinant role of the wavelet mathematical modelling. |
GSE2817.qdab |
| GSE28367 |
Expression and SNP data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative |
This SuperSeries is composed of the SubSeries listed below. |
GSE28367.qdab |
| GSE28618 |
Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells |
HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies. In this study, we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunocytochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression of HOXD9 in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs). Our results suggest that HOXD9 may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target. |
GSE28618.qdab |
| GSE28642 |
Non-phosphorylated FTY720 induces apoptosis of human microglia by activating SREBP2 |
A synthetic analog of sphingosine named FTY720 (Fingolimod), phosphorylated by sphingosine kinase-2, interacts with sphingosine-1-phosphate (S1P) receptors expressed on various cells. FTY720 suppresses the disease activity of multiple sclerosis (MS) chiefly by inhibiting S1P-dependent egress of autoreactive T lymphocytes from secondary lymphoid organs, and possibly by exerting anti-inflammmatory and neuroprotective effects directly on brain cells. However, at present, biological effects of FTY720 on human microglia are largely unknown. We studied FTY720-mediated apoptosis of a human microglia cell line HMO6. The exposure of HMO6 cells to non-phosphorylated FTY720 (FTY720-non-P) induced apoptosis in a dose-dependent manner with IC50 of 10.6±2.0 microM, accompanied by the cleavage of caspase-7 and caspase-3 but not of caspase-9. The apoptosis was inhibited by Z-DQMD-FMK, a caspase-3 inhibitor, but not by Pertussis toxin, a Gi protein inhibitor, suramin, a S1P3/S1P5 inhibitor, or W123, a S1P1 competitive antagonist, although HMO6 expressed S1P1, S1P2, and S1P3. Furthermore, both phosphorylated FTY720 (FTY720-P) and SEW2871, a S1P1 selective agonist did not induce apoptosis of HMO6. Genome-wide gene expression profiling and molecular network analysis indicated activation of transcriptional regulation by sterol regulatory element-binding protein (SREBP) in FTY720-non-P-treated HMO6 cells. Western blot verified activation of SREBP2 in these cells, and apoptosis was enhanced by pretreatment with simvastatin, an activator of SREBP2, and by overexpression of the N-terminal fragment of SREBP2. These observations suggest that FTY720-non-P-induced apoptosis of HMO6 human microglia is independent of S1P receptor binding, and positively regulated by the SREBP2-dependent proapoptotic signaling pathway. |
GSE28642.qdab |
| GSE2864 |
tourt-affy-human-131547 |
Nerve growth factor (NGF) is a neurotrophin that plays an important role in regulating the survival, growth, and differentiation of sympathetic neurons. Many in vitro studies indicate that Egr transcription factors are coupled to NGF signaling and are essential signaling mediators of NGF-dependent differentiation of sympathetic neurons, such as neuroblastoma cells and pheochromocytoma cells. Mice that are deficient for both Egr1 and Egr3 have profound sympathetic nerve system defects, including abnormal neuron degeneration and impaired differentiation (unpublished observations). To further understand the role of Egr genes in sympathetic neuron development, it is necessary to examine the signal transduction pathways involved in NGF-mediated Egr-dependent gene regulation. The results will be helpful in understanding the pathobiology of those diseases related to aberrant sympathetic neuron differentiation, such as neuroblastoma and dysautonomias, and may provide new insights into therapies for these refractory diseases. |
GSE2864.qdab |
| GSE29140 |
An extreme human-specific delay in cortical synaptic development |
This SuperSeries is composed of the SubSeries listed below. |
GSE29140.qdab |
| GSE29237 |
Optic Vesicle Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment |
Microarray anlaysis was performed to investigate gene expression patterns of other transcription factors involved in early retinal and/or forebrain development using human embryonic stem cell-derived retinal and forebrain progenitor cells. After 20 days of differentiation, vesicular neurospheres selectively expressed multiple retinal transcription factor genes appropriate for the OV stage of retinogenesis, whereas nonvesicular neurospheres expressed transcription factors indicative of the embryonic forebrain. Many transcription factor genes associated with retinal development were present at higher levels in vesicular vs. nonvesicular neurospheres. Nonvesicular neurospheres, on the other hand, expressed higher levels of transcription factors implicated in early forebrain development. Taken together, results indicated that the vesicular and nonvesicular neurospheres harbored retinal progenitor cells and early forebrain populations, respectively. |
GSE29237.qdab |
| GSE29368 |
CD140a+ human oligodendrocyte progenitor cells |
Glial progenitor cells (GPCs) pervade the human brain. These cells express gangliosides recognized by MAb A2B5, and some but not all can generate oligodendrocytes. Since some A2B5+ GPCs express PDGFa receptor (PDGFRa), which is critical to oligodendrocyte development, we asked if PDGFRa-directed sorting might isolate oligodendrocyte-competent progenitors. We used FACS to sort PDGFRa+ cells from the second trimester fetal human forebrain, based on expression of the PDGFRa epitope CD140a. CD140a+ cells could be maintained as mitotic progenitors that could be instructed to either oligodendrocyte or astrocyte phenotype. Transplanted CD140a+ cells robustly myelinated the hypomyelinated shiverer mouse brain. Microarray confirmed that CD140a+ cells differentially expressed PDGFRA, NG2, OLIG1/2, NKX2.2 and SOX2. Some expressed CD9, thereby defining a CD140a+/CD9+ fraction of oligodendrocyte-biased progenitors. CD140a+ cells differentially expressed genes of the PTN-PTPRZ1, wnt, notch and BMP pathways, suggesting the interaction of self-renewal and fate-restricting pathways in these cells, while identifying targets for their mobilization and instruction. |
GSE29368.qdab |
| GSE29384 |
Tetracycline-Inducible Cyr61 effect on LN229 glioma cells |
Glioblastoma multiforme is the most common and aggressive form of brain cancer. The use of oncolytic HSV-1 (oHSV) to selectively target brain cancer cells leading to their lytic destruction has shown to be very promising in a preclinical setting, but is lacking efficacy in clinical trials. Cyr61, a secreted extracellular matrix protein which functions to promote angiogenesis, migration, proliferation and tumorigenesis, was found to be upregulated rapidly following oHSV infection. Here we show, using microarray analysis, that Cyr61 expression leads to the induction of several genes with type 1 interferon function. We show that Cyr61 mediated type 1 IFN induction is through its interaction with integrin alpha6beta1 on the cell surface and results in oHSV inhibition, reducing the efficacy of this therapy. |
GSE29384.qdab |
| GSE29494 |
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival |
Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients. |
GSE29494.qdab |
| GSE29652 |
Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype |
Astrocyte dysfunction impacts their normal function, including neuronal support, thereby contributing to neurodegenerative pathologies including Alzheimer's disease (AD). Therefore to understand the role of astrocytes in the pathogenesis of age-related disorders we analysed the gene expression profile of astrocytes with respect to Alzheimer-type pathology. |
GSE29652.qdab |
| GSE29796 |
Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes. |
Glial progenitor cells (GPCs) of the adult human white matter, which express gangliosides recognized by monoclonal antibody A2B5, are a potential source of glial tumors of the brain. We used A2B5-based sorting to extract progenitor-like cells from a range of human glial tumors, that included low-grade glioma, oligodendroglioma, oligo-astrocytomas, anaplastic astrocytoma, and glioblastoma multiforme. The A2B5+ tumor cells proved tumorigenic upon orthotopic xenograft, and the tumors generated reflected the phenotypes of those from which they derived. |
GSE29796.qdab |
| GSE30448 |
Transcriptional effect of an off-target shRNA targeting nucleostemin in human glioblastoma-derived cancer stem cells |
Glioblastomas (GBM) may contain a variable proportion of active cancer stem cells (CSCs) capable of self-renewal, of aggregating into CD133+ neurospheres, and to develop intracranial tumors that phenocopy the original ones. We hypothesized that nucleostemin may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. Here we report that nucleostemin is expressed in GBM-CSCs isolated from patient samples. The significance of its expression was addressed by targeting the corresponding mRNA using lentivirally transduced short hairpin RNA (shRNA). We found that an off-target nucleostemin RNAi (shRNA22) abolishes proliferation and induces apoptosis in GBM-CSCs. Furthermore, in the presence of shRNA22, GBM-CSCs failed to form neurospheres in vitro or grow on soft agar. When these cells are xenotransplanted into the brains of nude rats, tumor development is severely compromised. Attempts were made to identify the primary target of shRNA22, suggesting a transcription factor involved in one of the MAP-kinases signaling-pathways. The use of this shRNA may offer a new therapeutic approach for this incurable type of brain tumors. |
GSE30448.qdab |
| GSE30563 |
Gene Expression data from human brain tumor or normal brain |
Stem cells from various lineages have well known for its migration tendency toward glioma and become attractive vehicles to deliver therapeutic genes to brain tumors. However, which factors and mechanisms work in these function is not yet known. To identify those factors and mechanisms, we analyzed the brain tumor-specific gene expression profile using microarray analysis |
GSE30563.qdab |
| GSE30643 |
Expression data from parietal cortex of G114V genetic Creutzfeldt-Jakob disease patient |
The familial or genetic Creutzfeldt-Jakob disease (fCJD or gCJD) is the inherent form of human prion diseases, which accounts for approximately 10-15% of human prion diseases that are caused by mutations of the prion protein gene (PRNP). In this study, the global expression patterns of the parietal cortex from a patient with G114V gCJD were comparatively analyzed with the normal controls by using a commercial human genome expression chip. Totally 8774 genes showed differential expression, among them 2769 genes were upregulated and 6005 ones were downregulated. The reliability of the results was confirmed by the real-time RT-PCR assays for several specific genes. The most differentially expressed genes involved in the functions of regulation of transcription, ion transport, transcription, cell adhesion, signal transduction. The gene associated with gliosis was upregulated and the genes marked for neurons were downregulated, while the transcription of PRNP gene maintained unchanged. 169 different pathways showed significantly changed in the brain of G114V gCJD. The most significantly regulated pathways included that of Alzheimer’s and Parkinson’s disease, oxidative phosphorylation, regulation of actin cytoskeleton, MAPK signaling pathway and proteasome, which were described in prion diseases previously. In addition, some rarely addressed pathways in prion diseases, such as axon guidance, gap junction and purine metabolism, were also significantly changed in G114V gCJD. The transcriptional situations of the most genes in the top ten changed pathways were down-regulated. The extensive reductions of gene expressions in G114V gCJD showed the comparable profiles with sporadic CJD. The data here raised the useful clues for understanding the pathogenesis of the disease and selecting the potential biomarkers for diagnostic and therapeutic tools. |
GSE30643.qdab |
| GSE3064 |
X linked dystonia parkinsonism |
Investigation of expression profile in XDP brains. |
GSE3064.qdab |
| GSE30792 |
Expression data from Parkinson's iPSCs with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative |
A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding ?-synuclein. ?-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double ?-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of ?-synuclein, and for mechanistic experiments to study PD pathogenesis. |
GSE30792.qdab |
| GSE31122 |
Histone deacetylase inhibition decreases proliferation and potentiates the effect of ionizing radiation in atypical teratoid/rhabdoid tumor cells |
Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant CNS neoplasm whichprimarily occurs in children under three years of age. Due to poor outcomes with intense and toxicmultimodality treatment, new therapies are urgently needed. Histone deacetylase inhibitors (HDIs)have been evaluated as novel agents for multiple malignancies and have been shown to function asradiosensitizers. They act as epigenetic modifiers and lead to re-expression of inappropriatelyrepressed genes, proteins, and cellular functions. Due to the underlying chromatin remodeling genemutation in ATRT, HDIs are ideal candidates for therapeutic evaluation. To evaluate the role of HDIsagainst ATRT in vitro, we assessed the effect of drug treatment on proliferation, apoptosis, and geneexpression. Additionally, we examined HDI pretreatment as a radiosensitization strategy for ATRT.MTS and clonogenic assays demonstrated that HDI treatment significantly reduces the proliferativecapacity of BT-12 and BT-16 ATRT cells. Also, the HDI SNDX-275 was able to induce apoptosis in bothcell lines and induced p21Waf1/Cip1 protein expression as measured by Western blot. Evaluation ofdifferential gene expression by microarray and pathway analysis after HDI treatment demonstratedalterations of several key ATRT cellular functions. Finally, we showed that HDI pretreatmenteffectively potentiates the effect of ionizing radiation on ATRT cells as measured by clonogenic assay.These findings suggest that the addition of HDIs to ATRT therapy may prove beneficial, especiallywhen administered in combination with current treatment modalities such as radiation. |
GSE31122.qdab |
| GSE31545 |
Stem-like glioma-propagating cells contribute to molecular heterogeneity and survival outcome in oligodendroglial tumors |
Brain tumors are among the most malignant cancers and can arise from neural stem cells or oligodendrocyte progenitor cells (OPCs). Glioma-propagating cells (GPCs) that have stem-like properties have been derived from tumor variants such as glioblastoma multiforme (GBM) and oligodendroglial tumors, the latter being more chemosensitive with better prognosis. It has been suggested that such differences in chemosensitivity arise from the different profiles of OPCs versus neural stem cells. We thus explored if GPCs derived from these glioma variants can serve as reliable in vitro culture systems for studies. We utilized gene expression analyses, since GBM and oligodendrogliomas can be molecularly classified. Accordingly, we derived a gene signature distinguishing oligodendroglial GPCs from GBM GPCs collated from different studies, which was enriched for the Wnt, Notch and TGF-beta pathways. Using a novel method in glioma biology, the Connectivity Map, we mapped the strength of gene signature association with patient gene expression profiles in 2 independent glioma databases [GSE16011, http://caintegrator-info.nci.nih.gov/rembrandt]. Our gene signature consistently stratified survival in glioma patients. This data would suggest that in vitro low passage GPCs are similarly driven by transcriptomic changes that characterize the favorable outcome of oligodendrogliomas over GBM. Additionally, the gene signature was associated with the 1p/19q co-deletion status, the current clinical indicator of chemosensitivity. Our gene signature detects molecular heterogeneity in oligodendroglioma patients that cannot be accounted for by histology or the 1p/19q status alone, and highlights the limitation of morphology-based histological analyses in tumor classification, consequently impacting on treatment decisions. |
GSE31545.qdab |
| GSE32197 |
Predicted signaling pathways involved in the pathogenesis of meningiomas and EGFL6 as a potential novel serum biomarker for benign meningiomas |
Purpose: In this study, we try to investigate the possible signaling pathways involved in the tumorigenesis of fibroblastic and anaplastic meningiomas. We also attempt to investigate EGFL6 gene expression in brain arachnoidal tissues and various tumors and to measure EGFL6 levels in serum samples from healthy people and patients with various tumors by using ELISA. Experimental Design: Differential gene expression profiles between meningiomas and brain arachnoidal tissues were established by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis was performed to identify potential gene pathways that may be involved in the pathogenesis of meningiomas. Quantitative real-time PCR (qRT-PCR) was performed to validate the differentially expressed genes in the KEGG pathways. EGFL6 mRNA levels were also determined in brain arachnoidal tissues, meningiomas, and other tumors by qRT-PCR. EGFL6 levels were measured in serum samples from healthy people and patients with various tumors by using ELISA. Results: Fibroblastic meningioma exhibited upregulated PI3K/Akt and TGF? signaling pathways, and accelerated G1/S progression cell cycle. KEGG analysis also demonstrated that focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. Benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissues and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in all other investigated tumors. EGFL6 was hardly detectable in serum samples of healthy people. The mean serum EGFL6 concentration was 675, 118, and 126 pg/ml in patients with benign, atypical, and anaplastic meningiomas respectively. Patients with ovarian cancers also had high serum EGFL6 levels (mean concentration: 617 pg/ml). Patients with all other investigated tumors, however, had low levels of serum EGFL6 with mean concentration less than 240 pg/ml. Conclusion: We proposed that deregulation of cell cycle and PI3K/Akt pathways might play important roles in the tumorigenesis of fibroblastic meningioma. It was also suggested that the activated integrin-mediated signaling pathways were involved in the pathogenesis of anaplastic meningioma. We presented evidence that EGFL6 might serve as a novel serum biomarker for benign meningioma and ovarian cancer. It was also suggested that EGFL6 could help discriminate benignancy or malignancy of meningiomas before surgery or at early time points. |
GSE32197.qdab |
| GSE32482 |
Gene expression profiles of Glioblastoma stem cells in which ALK or pleiotrophin expression was suppressed. |
Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells. Anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for maintaining the stem-like properties and tumorigenicity of glioblastoma stem cells. |
GSE32482.qdab |
| GSE32534 |
Expression data of FFPE peritumoral neocortex tissue |
Epilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. However, the molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. The alteration in peritumoral microenvironments is believed to play a significant role in inducing epileptogenesis. |
GSE32534.qdab |
| GSE32876 |
Inferring transcriptional and microRNA-mediated regulatory programs in glioblastoma |
Large-scale cancer genomics projects are profiling hundreds of tumors at multiple molecular layers, including copy number, mRNA and miRNA expression, but the mechanistic relationships between these layers are often excluded from computational models. We developed a supervised learning framework for integrating molecular profiles with regulatory sequence information to reveal regulatory programs in cancer, including miRNA-mediated regulation. We applied our approach to 320 glioblastoma profiles and identified key miRNAs and transcription factors as common or subtype-specific drivers of expression changes. We confirmed that predicted gene expression signatures for proneural subtype regulators were consistent with in vivo expression changes in a PDGF-driven mouse model. We tested two predicted proneural drivers, miR-124 and miR-132, both underexpressed in proneural tumors, by overexpression in neurospheres and observed a partial reversal of corresponding tumor expression changes. Computationally dissecting the role of miRNAs in cancer may ultimately lead to small RNA therapeutics tailored to subtype or individual. |
GSE32876.qdab |
| GSE33109 |
Gene expression changes in human neural cells exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate) |
Organophosphorus compounds may induce neurotoxicity through mechanisms other than the cholinergic pathway, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. |
GSE33109.qdab |
| GSE33588 |
Human-specific patterns of gene expression in the brain |
This SuperSeries is composed of the SubSeries listed below. |
GSE33588.qdab |
| GSE33903 |
Expression array of peripheral neuro-ectodermal cell lines |
To study differentially expressed genes in neuro-ectodermal cell lines |
GSE33903.qdab |
| GSE34152 |
Expression data from GBM and normal neural CD133+ and CD133- cells |
We use gene expression data to provide a three-faceted analysis on the links between molecular subclasses of glioblastima, epithelial-to mesenchymal transition (EMT) and CD133 cell surface protein. The contribution of this paper is three-folded: First, we used a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrated that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between the genes up-regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provided evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we studied the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrated that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM demonstrates similarity with the signatures of both EMT and CD133, it also demonstrates some differences with each of these signatures that is partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together this data sheds light on role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme. |
GSE34152.qdab |
| GSE34234 |
Microarrays analysis of anti-Enterovirus 71 activity of Heparin |
We have previously shown that Heparin (Hep) significantly inhibited Enterovirus 71 (EV71) infection and binding in both Vero and a human neural cell line, SK-N-SH, in vitro. Therefore, in this study we intended to gain insight into the cellular and molecular mechanisms of action of Hep against clinical EV71 infection in neural cells. Instead of stating a long list of gene functions and pathways, we tried to select for EV71-induced genes that were exclusively affected by antiviral activity of Hep through a multi-level comparison and characterization. |
GSE34234.qdab |
| GSE34331 |
A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates. |
Injury to the central nervous system (CNS) may result in lifelong loss of function due, in part, to the regenerative failure of CNS neurons. Major barriers to regeneration faced by injured CNS neurons include inhibitory proteins derived from myelin and the astroglial scar. Previously, we described the identification of a novel compound, F05, which promotes neurite growth from neurons challenged with inhibitory substrates in vitro, and promotes axonal regeneration in vivo (Usher et al., 2010). To identify additional regeneration promoting compounds, we used the microarray derived gene expression signature of F05 to query the Broad Institute Connectivity Map, a database of gene expression profiles for cells treated with >1,300 compounds. Unexpectedly, F05 induced changes in gene expression remarkably similar to those seen with a group of piperazine phenothiazine antipsychotics (PhAPs). We found that, in contrast to antipsychotics of other structural classes, PhAPs were able to promote neurite growth of CNS neurons cultured on two different glial-derived inhibitory substrates, but did not promote growth on a permissive substrate. Pharmacological studies suggest that the ability of PhAPs to promote growth depends on antagonism of calmodulin signaling, but not on dopamine receptor antagonism. Our findings shed light on mechanisms underlying neurite-inhibitory signaling, and suggest a potential pathway for development of novel treatments for CNS injury. |
GSE34331.qdab |
| GSE34516 |
Brain transcriptomic profiling in idiopathic and LRRK2-associated Parkinson's disease |
LRRK2 mutations are the most common genetic cause of Parkinson’s disease (PD). We performed a whole-genome RNA profiling of locus coeruleus post-mortem tissue from idiopathic PD (IPD) and LRRK2-associated PD patients. The differentially expressed genes found in IPD and LRRK2-associated PD were involved in the gene ontology terms of synaptic transmission and neuron projection. In addition, in the IPD group we found associated genes belonging to the immune system. Pathway analysis of the differentially expressed genes in IPD was related with neuroactive-ligand receptor interaction and with immune system pathways. Specifically, the analysis highlighted differential expression of genes located in the chromosome 6p21.3 belonging to the class II HLA. Our findings support the hypothesis of a potential role of neuroinflammation and the involvement of the HLA genetic area in IPD pathogenesis. Future studies are necessary to shed light on the relation of immune system related pathways in the etiopathogenesis of PD. |
GSE34516.qdab |
| GSE34551 |
NPTX1 is a Critical Regulator of Neural Induction in Human Pluripotent Stem Cells |
NPTX1 is a key inducer of neural lineages from the human ESC. |
GSE34551.qdab |
| GSE34771 |
Expression data from primary central nervous system lymphoma (PCNSL) patients |
This study aimed to define the genes associated with PCNSL patient survival. Expression profiling was performed on 34 PCNSLs. A gene classifier was developed. |
GSE34771.qdab |
| GSE35218 |
Nanomolar treatment with epigenetic drug combination induces genome-wide methylation and expression alterations in neuro-ectodermal cell lines [mRNA] |
Abstract: Epigenetic alterations are a fundamental aspect of cancer cells, and epigenetic drugs are currently used in clinical practice for hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and show epigenetic defects of apoptotic pathways, which makes the introduction of epigenetic drugs in this patient category logical. However, the young age of these patients is accompanied by ongoing developmental processes which are regulated epigenetic mechanisms, and prompted us to study molecular effects of nanomolar dosage epigenetic drugs in neuro-ectodermal tumor cell lines. Combination treatment of 5-aza-2'-deoxicytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages resulted in wide-spread demethylating effects in 17 NBL and 5 PNET cell lines in vitro. This widespread demethylation had large effects on gene-expression profiles. In NBL cell lines, almost every cellular pathway (193/200) investigated demonstrated altered expression upon treatment, and resulted in upregulation of known epigenetically regulated genes such as X-chromosomal, tissue-specific, and a few imprinted genes. Integration analysis of CpG island methylation array data and whole genome gene expression data identified 30 genes potentially upregulated by gene promoter demethylation. Homeobox genes frequently showed demethylation in both short term (72 hours) and long term cultures (3 months) of NBL lines. Continuous treatment with epigenetic drugs resulted in low rates of proliferation. The low rate of proliferation that might explain limited consecutive demethylation upon prolonged exposure. In conclusion, genome-wide methylation and gene expression changes are induced DAC and TSA treatment at nanomolar dosages. These effects affected more than 97% of cellular pathways investigated. Further studies towards the effects of epigenetic drug combinations are advised before being applied in clinical trials for pediatric patients. |
GSE35218.qdab |
| GSE35397 |
Host response and dysfunction in the CNS during chronic simian immunodeficiency virus infection |
Molecular basis for CNS dysfunction in simian immunodeficiency virus-infected rhesus monkeys. |
GSE35397.qdab |
| GSE35493 |
Pediatric rhabdoid tumors of kidney and brain show many differences in gene expression but share dysregulation of cell cycle and epigenetic effector genes |
Rhabdoid tumors (RTs) are aggressive tumors of early childhood that occur most often in brain (AT/RTs) or kidney (KRTs). Regardless of location, they are characterized by loss of functional SMARCB1 protein, a component of the SWI/SNF chromatin remodeling complex. The aim of this study was to determine genes and biological process dysregulated in common to both AT/RTs and KRTs. Gene expression for AT/RTs was compared to that of other brain tumors and normal brain using microarray data from our lab. Similar analysis was performed for KRTs and other kidney tumors and normal kidney using data from GEO. Dysregulated genes common to both analyses were analyzed for functional significance. Unsupervised hierarchical clustering of RTs identified 3 major subsets: 2 comprised of AT/RTs, and 1 of KRTs. Compared to other tumors, 1187, 663 and 539 genes were dysregulated in each subset, respectively. Only 14 dysregulated genes were common to all 3 subsets. Compared to normal tissue, 5209, 4275 and 2841 genes were dysregulated in each subset, with an overlap of 610 dysregulated genes. Among these genes, processes associated with cell proliferation, MYC activation, and epigenetic dysregulation were common to all 3 RT subsets. The low overlap of dysregulated genes in AT/RTs and KRTs suggests that factors in addition to SMARCB1 loss play a role in determining subsequent gene expression. Drugs which target cell cycle or epigenetic genes may be useful in all RTs. Additionally, targeted therapies tailored to specific RT subset molecular profiles should be considered. |
GSE35493.qdab |
| GSE35642 |
Transcriptome analysis of a chronic in vitro model of Parkinsonism |
The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs. |
GSE35642.qdab |
| GSE35864 |
The National NeuroAIDS Tissue Consortium Brain Gene Array: Two types of HIV-associated neurocognitive impairment |
Finding the differences in gene expression in three regions of the brain, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients. |
GSE35864.qdab |
| GSE35974 |
Expression data from the human cerebellum brain |
Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. Associated genetic and gene expression |
GSE35974.qdab |
| GSE35977 |
Expression data from the human parietal cortex brain |
Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. Associated genetic and gene expression |
GSE35977.qdab |
| GSE36145 |
Direct reprogramming of human astrocytes into neural stem cells and neurons |
Ectopic expression of the reprogramming factors OCT4, SOX2, or NANOG into human astrocytes in specific cytokine/culture conditions activated the neural stem gene program and induced generation of cells expressing neural stem/precursor markers. |
GSE36145.qdab |
| GSE36245 |
Gene expression data from glioblastoma tumor samples |
Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins. |
GSE36245.qdab |
| GSE36321 |
Gene expression analysis of H9 hESC derived neuron stem cells (NSC) harboring pathogenic LRRK2 (G2019S) mutation |
Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. |
GSE36321.qdab |
| GSE36619 |
Gene expression profile of U373MG exposed to novel anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids |
Background: Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a) and renieramycin M (RM; the compound 2a) from Thai marine invertebrates, together with a 2’-N-4”-pyridinecarbonyl derivative of ET-770 (ET-770-DR; the compound 3). We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG. Methods: We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. Results: All of these compounds dissolved in dimethyl sulfoxide (DMSO) as a vehicle induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ET-770 downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR) signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B. Conclusion: Molecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective drug targets. |
GSE36619.qdab |
| GSE36634 |
Fate determination of adult human glial progenitor cells |
Glial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function. |
GSE36634.qdab |
| GSE36678 |
Expression data SK-N-SH cells treated with risperidone |
We performed a pharmacotranscriptomic analysis of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. |
GSE36678.qdab |
| GSE36782 |
Glioma-propagating cells as an in vitro screening platform: PLK1 as a case study |
Gliomas are the most devastating of primary adult malignant brain tumors. These tumors are highly infiltrative and can arise from cells with extensive self-renewal capability and chemoresistance, frequently termed glioma-propagating cells (GPCs). GPCs are thus the plausible culprits of tumor recurrence. Treatment strategies that eradicate GPCs will greatly improve disease outcome. Such findings support the use of GPCs as in vitro cellular systems for small molecule screening. However, the nuances in utilizing GPCs as a cellular screening platform are not trivial. These slow-growing cells are typically cultured as suspension, spheroid structures in serum-free condition supplemented with growth factors. Consequently, replenishment of growth factors throughout the screening period must occur to maintain cells in their undifferentiated state, as the more lineage-committed, differentiated cells are less tumorigenic. We will present a case study of a small molecule screen conducted with GPCs and explain how unique sphere activity assays were implemented to distinguish drug efficacies against the long-term, self-renewing fraction, as opposed to transient-amplifying progenitors, latter of which are detected in conventional viability assays. We identified Pololike kinase 1 as a regulator of GPC survival. Finally, we leveraged on public glioma databases to illustrate GPC contribution to disease progression and patient survival outcome. |
GSE36782.qdab |
| GSE36980 |
Expression data from post mortem Alzheimer's disease brains |
To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) |
GSE36980.qdab |
| GSE37418 |
Novel mutations target distinct subgroups of medulloblastoma. |
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. |
GSE37418.qdab |
| GSE37923 |
Functional expression of membrane alanyl-aminopeptidase (CD13/APN) promotes tumor cell proliferation and neoangiogenesis in malignant gliomas. |
Malignant gliomas are characterized by marked neovascularization and increased tumor cell proliferation. Recently, membrane alanyl-aminopeptidase (CD13/APN) has been identified to play a crucial role in neoangiogenesis. In this study, we show that among various central nervous system tumors, malignant astrocytomas are unique in their high expression levels of functionally active CD13/APN. CD13/APN was found in both tumor cells and tumor vessels of malignant astrocytomas, while in low-grade astrocytomas only endothelial cells of tumor vessels expressed CD13/APN. Inhibitors of the enzymatic activity of CD13/APN significantly reduced the proliferation of U87MG and U138MG malignant glioma cells. Inhibition of CD13/APN mRNA expression by siRNA in glioma cells co-cultured with human umbilical vein endothelial cells (HUVEC) effectively decreased blood vessel formation. Pro-angiogenic factors like bFGF and VEGF induced CD13/APN expression in glioma cells. Treatment of U87MG and U138MG cells with CD13/APN inhibitors resulted in an increased mRNA expression of VEGF and VEGF receptor 2 (VEGF-R2) in these cells. Taken together, these findings provide evidence that CD13/APN promotes tumor cell proliferation and blood vessel formation in malignant astrocytomas. Remarkably, inhibition of CD13/APN induces an angiogenic expression profile via an autocrine feed-back mechanism involving the VEGF/VEGF-R2 system in malignant gliomas. |
GSE37923.qdab |
| GSE37981 |
Molecular profiles of pyramidal cell dysfunction in the superior temporal cortex in schizophrenia |
Gray matter volume in the cerebral cortex has been consistently found to be decreased in patients with schizophrenia. The superior temporal gyrus (STG) is one of the cortical regions that exhibit the most pronounced volumetric reduction. This reduction is generally thought to reflect, at least in part, decreased number of synapses; the majority of these synapses are believed to be furnished by glutamatergic axon terminals onto the dendritic spines on pyramidal neurons. Pyramidal neurons in the cerebral cortex exhibit layer-specific connectional properties, providing neural circuit structures that support distinct aspects of higher cortical functions. For instance, dendritic spines on pyramidal neurons in layer 3 of the cerebral cortex are targeted by both local and long-range glutamatergic projections in a highly reciprocal fashion. Synchronized activities of pyramidal neuronal networks, especially in the gamma frequency band (i.e. 30-100 Hz), are critical for the integrity of higher cortical functions. Disturbances of these networks may contribute to the pathophysiology of schizophrenia by compromising gamma oscillation. This concept is supported by the following postmortem and clinical observations. First, the density of dendritic spines on pyramidal neurons in layer 3 of the cerebral cortex, including the STG, have been shown to be significantly decreased by 23-66% in subjects with schizophrenia. Second, consistent with these findings, the average somal area of these pyramidal cells is significantly smaller. Third, we have recently found that, in the prefrontal cortex, the density of glutamatergic axonal boutons, of which dendritic spines are their major targets, was significantly decreased by as much as 79% in layer 3 (but not layer 5) in subjects with schizophrenia. Finally, an increasing number of clinical studies have consistently demonstrated that gamma oscillatory synchrony is profoundly impaired in patients with schizophrenia. Furthermore, gamma impairment has been linked to the symptoms and cognitive deficits of the illness and the severity of these symptoms and deficits have in turn been associated with the magnitude of cortical gray matter reduction. Taken together, understanding the molecular underpinnings of pyramidal cell dysfunction will shed important light onto the pathophysiology of cortical dysfunction of schizophrenia. In order to gain insight into the molecular determinants of pyramidal cell dysfunction in schizophrenia, we combined LCM with Affymetrix microarray and high-throughput TaqMan®-based MegaPlex qRT-PCR approaches, respectively, to elucidate the alterations in messenger ribonucleic acid (mRNA) and microRNA (miRNA) expression profiles of these neurons in layer 3 of the STG. We found that transforming growth factor beta (TGF?) and BMP (bone morphogenetic proteins) signaling pathways and many genes that regulate extracellular matrix (ECM), apoptosis and cytoskeleton were dysregulated in schizophrenia. In addition, we identified 10 miRNAs that were differentially expressed in this illness; interestingly, the predicted targets of these miRNAs included the dysregulated pathways and gene networks identified by microarray analysis. Together these findings provide a neurobiological framework within which we can begin to formulate and test specific hypotheses about the molecular mechanisms that underlie pyramidal cell dysfunction in schizophrenia. |
GSE37981.qdab |
| GSE38010 |
Janus-Like Opposing Roles of CD47 in Autoimmune Brain Inflammation in Human and Mice |
Gene transcripts and proteins expressed during disease pathogenesis identify targets for therapy. We performed microarray analysis of histologically characterized multiple sclerosis (MS) brain lesions in comparison with control brain samples to identify differentially expressed molecules. We identified CD47 as a target of interest and studied its biology in MS and EAE. |
GSE38010.qdab |
| GSE38431 |
Gene expression from induced CB-derived neurons at different time of differentiation |
Gene expression from cord blood stem cells and respective derived neuronal cells at different times point of differentiation:CD133+ cells; |
GSE38431.qdab |
| GSE3960 |
Classification of neuroblastoma by integrating gene expression pattern with regional alterations in DNA copy number |
The specific genes that influence neuroblastoma biology and are targeted by genomic alterations remain largely unknown. We quantified mRNA expression in a highly annotated series of 101 prospectively collected diagnostic neuroblastoma primary tumors and the expression profiles were determined using Affymetrix U95Av2 arrays. Comparisons between the sample groups allow the identification of genes with localized expression patterns. This study demonstrates that the genomic data can be used to subcategorize the disease into molecular subsets and the regional copy number alterations are correlated with a broad number of transcriptional alterations genome wide. This data also suggests that multiple genes from several discrete regions of the human genome co-operate to supress neuroblastoma tumorigenesis and progression. |
GSE3960.qdab |
| GSE39645 |
Microarray Analysis in Vestibular Schwannomas |
Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. |
GSE39645.qdab |
| GSE40102 |
Comparing Control and Schizophrenic hiPSC-derived NPCs |
Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia (SCZD) generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SCZD brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SCZD might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SCZD patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SCZD hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes, reduced WNT signaling and aberrant cellular migration. |
GSE40102.qdab |
| GSE4030 |
bunge-affy-arabi-162779 |
Schwann cells, expanded in number by exposure to growth factors in vitro, could be useful in nervous system repair. Our previous results suggest that long term exposure to heregulin and forskolin changes the functional properties of the human Schwann cells, including the ability to myelinate axons after transplantation. Here, we propose to determine the molecular changes in the Schwann cells that occur as a result of extended growth with mitogenic factors. We believe that the information obtained in these studies will provide clues about mechanisms underlying the already observed changes in function. This information will aid in the prediction of the safety and efficacy of neural repair approaches that use cultured, expanded Schwann cells. Finally this data may provide clues into the mechanisms underlying normal human Schwann cell function. |
GSE4030.qdab |
| GSE4036 |
perro-affy-human-186940 |
Our laboratory has developed the first mouse model overexpressing a RNA-binding protein, the ELAV-like protein HuD, in the CNS under the control of the CaMKinII alpha promoter. Initial behavioral characterization of the mice revealed that they had significant learning deficits together with abnormalities in prepulse inhibition (PPI). At the molecular level, we found that the expression of the growth-associated protein GAP-43, one of the targets of HuD, was increased in the hippocampus of HuD transgenic mice. To characterize these mice further and to evaluate the utility of these animals in understanding human diseases, we propose to use DNA microarray methods. |
GSE4036.qdab |
| GSE40438 |
Gene expression profiling of resistant and vulnerable motor neuron subtypes in amyotrophic lateral sclerosis |
A consistent clinical feature of amyotrophic lateral sclerosis (ALS) is the sparing of eye movements. Pathological studies have confirmed that there is relative sparing of the cranial motor nuclei of the oculomotor, trochlear and abducens nerves, although pathological changes resembling those seen in anterior horn cells are present to a lesser degree. The aim of the present study is to combine LCM and microarray analysis to study the differences between motor neurons that are selectively resistant (oculomotor neurons) and those that are vulnerable (lumbar spinal motor neurons) to the disease process in amyotrophic lateral sclerosis. |
GSE40438.qdab |
| GSE40695 |
Expression data from NSCs treated with REST inhibitor X5050 |
REST has been initially described as a repressor of neuronal genes in non-neuronal cells by binding to its recognition sequence RE1. Over-activation of this factor has been shown in several diseases such as Huntington disease or central nervous system cancers. High-throughput screening of a library of 6,984 compounds with luciferase-assay measuring REST activity in neural derivatives of human embryonic stem cells led to the identification of one benzoimidazole-5-carboxamide derivative (X5050) that inhibited REST silencing in a RE1-dependent manner. |
GSE40695.qdab |
| GSE40749 |
Expression data from hiPSCs-NSCs towards U87 |
Neural stem cells can migrate towards tumors of both neural and non-neural origins, which is crucial for the success in treating disseminated tumors. Although the understanding of the molecular mechanisms underlying NSC tumor tropism is limited, it has been noted that several cytokines, growth factors and receptors direct the migration in vitro. A proper understanding of the basic molecular mechanisms of NSC migration towards tumors, especially identification of key cellular regulators of the migration, will have important implications in improving the effectiveness of engineering and employing NSCs as tumor therapy agents. |
GSE40749.qdab |
| GSE40750 |
Expression data from hiPSCs-NSCs towards 4T1 |
Neural stem cells can migrate towards tumors of both neural and non-neural origins, which is crucial for the success in treating disseminated tumors. Although the understanding of the molecular mechanisms underlying NSC tumor tropism is limited, it has been noted that several cytokines, growth factors and receptors direct the migration in vitro. A proper understanding of the basic molecular mechanisms of NSC migration towards tumors, especially identification of key cellular regulators of the migration, will have important implications in improving the effectiveness of engineering and employing NSCs as tumor therapy agents. |
GSE40750.qdab |
| GSE40751 |
Inhibition of neuronal nitric oxide synthase activity promotes migration of human induced pluripotent stem cell-derived neural stem cells towards cancer cells |
This SuperSeries is composed of the SubSeries listed below. |
GSE40751.qdab |
| GSE40865 |
Global gene expression analysis for neuron stem cells (NSC) derived from iPSCs with Fanconi Anemia |
Fanconi Anemia (FA) is a recessive disorder associated with genomic instability |
GSE40865.qdab |
| GSE40904 |
Gene expression analysis for Il13Ra2-positive and IL13Ra2-negative glioma cell lines |
Affymetrix expression profiling was used to evaluate the association between IL13R?2 expression, and mesenchymal, proneural, classical and neural signature genes expression for glioma subclasses defined by Verhaak et al (Cancer Cell; 2010). |
GSE40904.qdab |
| GSE41842 |
Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway |
Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes. |
GSE41842.qdab |
| GSE42294 |
Identification of BORIS-bound transcripts in neural progenitor cells and young neurons |
This study compares the transcripts bound to BORIS in neural progenitor cells and cells differentiated for 6 days into young neurons |
GSE42294.qdab |
| GSE4271 |
Molecular subclasses of high-grade glioma: prognosis, disease progression, and neurogenesis |
Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006. |
GSE4271.qdab |
| GSE42762 |
FOXO3a Is A Major Target Of Inactivation By PI3K/AKT Signaling In Aggressive Neuroblastoma |
Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. |
GSE42762.qdab |
| GSE43209 |
The landscape of somatic alterations in epigenetic genes across 21 pediatric cancers |
As a part of the St Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project (PCGP), we adapted deep sequencing technologies and have sequenced 1025 tumor samples from 21 diseases covering brain, solid tumors and leukemias. We analyzed the genomic DNA sequences, copy number variations and structural rearrangements of 633 genes whose proteins are involved in epigenetic machineries, including those that covalently modify DNA and histones, and structurally reorder chromatin. To examine gene expression level of mutated histone genes, we analyzed gene expression in a group of 40 non-ETP T-lineage ALL samples using Affymetrix GeneChip HT HG-U133+ PM arrays (including 37 samples deposited in GSE28703 and 3 additional arrays not studied previously). The results provide us the knowledge of potential therapeutic targets for pediatric cancer treatment and improvement of personalized therapy. |
GSE43209.qdab |
| GSE43235 |
Human embryonic stem cells differentiated in dopaminergic neurons |
Human embryonic stem cells have been a great interest due to its potential to provide a renewable source of surrogate dopamine neurons for transplantation into Parkinson’s disease patients. We have differentiated hESCs with a monolayer of PA6 cells under 2D and 3D systems for 28 days. Genome-wide microarray analysis showed that our 3D samples increased expression of genes that are involved in neuronal developments such as Wnt, hedgehog and mitogen-activated protein kinase (MAPK) signalling pathways. The results suggest that the 3D differentiation system may have affected the regulatory or signalling mechanisms which enhanced the rate of differentiation towards ectoderm. |
GSE43235.qdab |
| GSE43326 |
Gene expression data from iPSC-derived neural cells, comparison between APP wild and E693delta mutation |
Oligomeric forms of amyloid-beta peptide (Abeta) are presumed to play a pivotal role in the pathogenesis of Alzheimer’s disease (AD). However, it is still unclear how Abeta oligomers contribute to AD pathogenesis in patient neural cells. We generated induced pluripotent stem cells (iPSCs) from a familial AD patient and differentiated them into neural cells. Abeta oligomers were accumulated in neural cells of AD bearing amyloid precursor protein (APP)-E693delta mutation. |
GSE43326.qdab |
| GSE43392 |
Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition |
Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically-defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis demonstrated downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knock-down phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in three in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma. |
GSE43392.qdab |
| GSE43552 |
Expression profiling of human medulloblastoma cell line ONS76 upon siRNA-mediated knockdown of KDM5A/LSD1 |
KDM5A/LSD1 is an important epigenetic regulator in medulloblastoma, the most frequent brain tumor of childhood. Here, the response of ONS76 medulloblastoma cells upon siRNA-mediated knockdown of KDM5A is analysed. |
GSE43552.qdab |
| GSE43794 |
Differentiation of human fetal multipotential neural progenitor cells to astrocytes reveals susceptibility factors for JC Virus |
Viral infections of the CNS are of increasing concern, especially among immunocompromised populations. Rodent models are often inappropriate for studies of CNS infection, as many viruses, including JC Virus (JCV) and HIV, cannot replicate in rodent cells. Consequently, human fetal brain-derived multipotential CNS progenitor cells (NPCs) that can be differentiated into neurons, oligodendrocytes, or astrocytes, have served as a model for CNS studies. NPCs can be non-productively infected by JCV, while infection of progenitor-derived astrocytes (PDAs) is robust. We profiled cellular gene expression at multiple times during differentiation of NPCs to PDAs. Several activated transcription factors show commonality between cells of the brain in which JCV replicates and lymphocytes in which JCV is likely latent. Bioinformatic analysis determined transcription factors that may influence the favorable transcriptional environment for JCV in PDAs. This study attempts to provide a framework for understanding the functional transcriptional profile necessary for productive JCV infection. |
GSE43794.qdab |
| GSE4412 |
freij-affy-human-91666 |
Diffuse infiltrating gliomas are the most common primary brain malignancy found in adults, and Glioblastoma multiforme, the highest grade glioma, is associated with a median survival of 7 months. Transcriptional profiling has been applied to 85 gliomas from 74 patients to elucidate glioma biology, prognosticate survival, and define tumor sub-classes. These studies reveal that transcriptional profiling of gliomas is more accurate at predicting survival than traditional pathologic grading, and that gliomas characteristically express coordinately regulated genes of one of four molecular signatures: neurogenesis, synaptic transmission, mitotic, or extra-cellular matrix. Elucidation of these survival associated molecular signatures will aid in tumor prognostication and define targets for future directed therapy. |
GSE4412.qdab |
| GSE44265 |
HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs. |
Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent. |
GSE44265.qdab |
| GSE44266 |
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders. |
Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders. |
GSE44266.qdab |
| GSE44456 |
Stress-response pathways are altered in the hippocampus of chronic alcoholics. |
Comparison of gene expression in post-mortem hippocampus from 20 alcoholics and 19 controls. |
GSE44456.qdab |
| GSE44537 |
Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas |
Cancer stem cells (CSCs) are plastic in nature, a characteristic that hampers cancer therapeutics. Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and half of the cases are highly aggressive. By treating NB cell lines (SKNAS, SKNBE(2)C, CHP134, SY5Y) with epigenetic modifiers for a short time followed by sphere-forming culture conditions, we have established stem cell-like NB cells that are phenotypically stable for over a year. These cells are characterized by their high expression of stemness factors, stem cell markers, and open chromatin structure. We referred to these cells as induced CSC (iCSC). SKNAS iCSC and SKNBE(2)C iCSC clones (as few as 100 cells) injected subcutaneously into SCID/Beige mice formed tumors, and in one case, SKNBE(2)C iCSC metastasized to the adrenal gland, suggesting their increased metastatic potential. SKNAS iCSC xenografts showed the histologic appearance of totally undifferentiated “large-cell” NBs (LCNs), the most aggressive and deadly form of NB in humans. Immunohistochemical analyses showed that SKNAS iCSC xenografts expressed high levels of the stem cell marker CXCR4, while the SKNAS monolayer cell xenografts did not. The patterns of CXCR4 and MYC expression in SKNAS iCSC xenografts resembled those in the LCNs. The xenografts established from the NB iCSCs shared two common features: the LCN phenotype and high-level MYC/MYCN expression. These observations suggest that NB cells with large and vesicular nuclei, representing their open chromatin structure, are indicative of stem cell-like tumor cells, and that epigenetic changes may have contributed to the development of these most malignant NB cells. |
GSE44537.qdab |
| GSE44541 |
Expression data from antimycin A-treated BE(2)-C cells |
Analysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with purified antimycin A1a or unfractionated commercially available antimycin A (Sigma A8674). |
GSE44541.qdab |
| GSE44971 |
Gene expression data from pilocytic astrocytoma tumour samples and normal cerebellum controls |
Pilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To further define their molecular development, we analysed the global DNA methylation profiles of 61 PAs and 6 normal cerebellum samples and integrated this data with transcriptome profiling. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Significant expression differences were identified for the majority of differentially methylated genes, and these were unexpectedly associated with a strong positive correlation between methylation and expression. We also identified a large number of differentially methylated/expressed genes between cerebellar PAs and normal cerebellum, which included additional developmental genes. |
GSE44971.qdab |
| GSE45437 |
Expression data from paediatric ependymoma short-term cell cultures |
Promoter hypermethylation and transcriptional silencing is a common epigenetic mechanism of tumour suppressor inactivation in cancer, including malignant brain tumours. |
GSE45437.qdab |
| GSE45587 |
Expression data for developing a GE-HTS signature for neuroblastoma differentiation |
Gene expression data from BE(2)-C cells treated in triplicate with either vehicle (DMSO), 5 ?M all-trans retinoic acid (ATRA), 1 mM valproic acid (VPA), or 5 ?M ATRA + 1 mM VPA for 6, 24, or 72 hours. Genome-wide expression profiling was performed using Affymetrix U133A microarrays. |
GSE45587.qdab |
| GSE45639 |
Clonal Immortalized Human Glial Cell Lines Support Varying Levels of JC Virus Infection due to Differences in Cellular Gene Expression |
JC virus (JCV) is a ubiquitous human polyomavirus that causes the demyelinating disease Progressive Multifocal Leukoencephalopathy (PML). JCV replicates in limited cell types in culture, predominantly in human glial cells. Thus, productive JCV infection is an indicator of the host cell transcription environment. Following introduction of a replication defective SV40 mutant that expressed large T protein into a heterogeneous culture of human fetal brain cells, multiple phenotypes became immortalized (SVG cells). A subset of SVG cells could support JCV replication. This mixed culture was called SVG cells. In the current study, clonal cell lines were selected from the original SVG cell culture. The SVG-5F4 clone showed low levels of viral growth. The SVG-10B1 clone was highly permissive for JCV DNA replication and gene expression. Microarray analysis revealed that viral infection did not significantly change gene expression in these cells. More resistant 5F4 cells expressed high levels of transcription factors known to inhibit JCV transcription. Interestingly, 5F4 cells highly expressed RNA of markers of Bergman or radial glia and 10B1 cells had high expression of markers of immature glial cells and activation of transcription regulators important for stem/progenitor cell self-renewal. These SVG-derived clonal cell lines provide a biologically relevant model to investigate cell type differences in JCV host range and pathogenesis, as well as neural development. |
GSE45639.qdab |
| GSE45921 |
Expression data from human glioma tissues |
Gliomas are aggressive lethal solid brain tumors arising from support cells in the central nervous system. Despite intense efforts to optimize the treatment of gliomas, the outcomes of high grade glioma patients are still frustrating. The causes and progress of gliomas have been investigated extensively; however, the genetic factors involved in the development of this disease remain poorly understood. |
GSE45921.qdab |
| GSE45967 |
Targeting Myc signaling pathway by inhibition of histone demethylase JMJD2B (siRNA) |
Epigenetic alterations appear to modulate Myc signaling. We investigated the role of the histone demethylase JMJD2B in Myc-mediated neuroblastoma pathogenesis. We demonstrate that Myc physically interacts with and recruits this epigenetic modifier, which removes repressive H3K9 methyl marks from Myc-target genes. JMJD2B regulates neuroblastoma proliferation and, together with MYCN amplification, identifies a subgroup of poor prognosis patients. We identify a novel histone demethylase inhibitor, ciclopirox, which targets JMJD2B and, consequently, Myc signaling, thereby inhibiting neuroblastoma proliferation and inducing differentiation. In xenograft studies, genetic and pharmacologic inhibition of JMJD2B resulted in significant tumor growth restriction. Our findings provide insight into epigenetic regulation of Myc via histone methylation and proof-of-concept for pharmacologic inhibition of histone demethylases to target Myc signaling in cancer. |
GSE45967.qdab |
| GSE45969 |
Targeting Myc signaling pathway by inhibition of histone demethylase JMJD2B (ciclopirox) |
Epigenetic alterations appear to modulate Myc signaling. We investigated the role of the histone demethylase JMJD2B in Myc-mediated neuroblastoma pathogenesis. We demonstrate that Myc physically interacts with and recruits this epigenetic modifier, which removes repressive H3K9 methyl marks from Myc-target genes. JMJD2B regulates neuroblastoma proliferation and, together with MYCN amplification, identifies a subgroup of poor prognosis patients. We identify a novel histone demethylase inhibitor, ciclopirox, which targets JMJD2B and, consequently, Myc signaling, thereby inhibiting neuroblastoma proliferation and inducing differentiation. In xenograft studies, genetic and pharmacologic inhibition of JMJD2B resulted in significant tumor growth restriction. Our findings provide insight into epigenetic regulation of Myc via histone methylation and proof-of-concept for pharmacologic inhibition of histone demethylases to target Myc signaling in cancer. |
GSE45969.qdab |
| GSE4600 |
Identifying targets of MeCP2 during neuronal maturational differentiation |
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG binding protein 2. MeCP2 is a transcriptional repressor elevated in mature neurons and is predicted to be required for neuronal maturation by regulating multiple target genes. Identifying primary gene targets in either Mecp2-deficient mice or human RTT brain has proven to be difficult, perhaps because of the transient requirement for MeCP2 during neuronal maturation. In order to experimentally control the timing of MeCP2 expression and deficiency during neuronal maturation, human SH-SY5Y cells undergoing mature neuronal differentiation were transfected with methylated MeCP2 oligonucleotide decoy to disrupt the binding of MeCP2 to endogenous targets. Genome-wide expression microarray analysis identified all four known members of the inhibitors of differentiation or inhibitors of DNA binding (ID1, ID2, ID3 and ID4) subfamily of helix-loop-helix (HLH) genes as novel neuronal targets of MeCP2. Chromatin immunoprecipitation analysis confirmed binding of MeCP2 near or within the promoters of ID1, ID2 and ID3, and quantitative RT-PCR confirmed increased expression of all four Id genes in Mecp2-deficient mouse brain. All four ID proteins were significantly increased in Mecp2-deficient mouse and human RTT brain using immunofluorescence and laser scanning cytometric analyses. Because of their involvement in cell differentiation and neural development, ID genes are ideal primary targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of RTT. |
GSE4600.qdab |
| GSE46235 |
Comparative expression data from HBVP (human brain vascular pericytes) and human MSC (mesenchymal stem cells) |
Pericytes and mesenchymal stem cells (MSC) are ontogenically related, and in fact no phenotypic differences were observed by flow cytometry using a panel of surface antigen markers. Global gene expression profiles of human pericytes and MSC revealed that 43 genes were expressed more than 10 fold in pericytes as compared to MSC. |
GSE46235.qdab |
| GSE46236 |
Expression data from LPS-treated HBVP (human brain vascular pericytes) |
Identification of TLR4 as one of the most abundant RNA species in pericytes with respect to MSC, and corroboration of TLR4 expression on the cell surface, led us to obtain a comprehensive overview of the expression program of lipopolysaccharide (LPS) stimulated pericytes. Microarray analyisis demonstrated the significant upregulation of 76 annotated genes including transcripts for adhesion molecules, inflammation mediators, pro-angiogenic factors, transcription factors and anti-apoptotic proteins. |
GSE46236.qdab |
| GSE46509 |
Molecular profile of parvalbumin-immunoreactive neurons in superior temporal cortex in schizophrenia |
Dysregulation of pyramidal cell network function by the soma- and axon-targeting inhibitory neurons that contain the calcium-binding protein parvalbumin (PV) represents a core pathophysiological feature of schizophrenia. In order to gain insight into the molecular basis of their functional impairment, we used laser capture microdissection (LCM) to isolate PV-immunolabeled neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem schizophrenia and normal control brains. We then extracted ribonucleic acid (RNA) from these neurons and determined their messenger RNA (mRNA) expression profile using the Affymetrix platform of microarray technology. 739 mRNA transcripts were found to be differentially expressed in PV neurons in subjects with schizophrenia, including genes associated with WNT (wingless-type), NOTCH and PGE2 (prostaglandin E2) signaling, in addition to genes that regulate cell cycle and apoptosis. Of these 739 genes, only 89 (12%) were also differentially expressed in pyramidal neurons as found in the accompanying study, suggesting that the molecular pathophysiology of schizophrenia appears to be predominantly neuronal type-specific. Taken together, findings of this study provide a neurobiological framework within which hypotheses of the molecular mechanisms that underlie the dysfunction of PV neurons in schizophrenia can be generated and experimentally explored and, as such, may ultimately inform the conceptualization of targeted molecular intervention. |
GSE46509.qdab |
| GSE47130 |
Vector-transduced neurons transcriptome profiles |
With the goal of specifically dissecting the toxicogenomic signatures of the helper-dependent (HD) human (HAd5) and canine (CAV-2) adenovirus, the VSV-G-pseudotyped SIN HIV-1 (LV) and the Adenoviral-associated vector 2/9 for human neurons (AAV2/9), we transduced a bona fide human neuronal system with HD-HAd5, HD-CAV-2, LV and AAV2/9, we analysed the transcriptional response of more than 47,000 transcripts using gene chips. |
GSE47130.qdab |
| GSE4755 |
torre-affy-human-217240 |
This project will help us to have a more accurate and useful explanation at molecular level, of the damage caused by HIV when it infects the central nervous sythem (CNS) in Humans. CNS dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus-I (HIV-1) infection and the acquired immunodeficiency virus syndrome (AIDS). Minor cognitive/motor dysfunction (MCMD) and HIV-1-associated dementia (HAD) develop in the absence of opportunistic infections and lymphoma, cerebrovascular disease and metabolic disorders. Patients with HAD may or may not present an associated HIV encephalitis with viral replication limited to cells of monocyte origin. The inflammatory infiltrates of HIVE include activated microglia and perivascular and parenchymal monocytes, multinucleated giant cells and lymphocytes. In addition, HIVE may be accompanied by significant loss of neurons, presynaptic terminals and abnormal dendrites. |
GSE4755.qdab |
| GSE4757 |
Alzheimer’s disease: neurofibrillary tangles (Rogers-3U24NS043571-01S1) |
Alzheimer's Disease (AD) is a devastating neurodegenerative disorder affecting approximately 4 million people in the U.S. alone. AD is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain. These pathological markers are thought to be responsible for the massive cortical neurodegeneration and concomitant loss of memory, reasoning, and often aberrant behaviors that are seen in patients with AD. Understanding the molecular mechanisms whereby these histopathological markers develop will greatly enhance our understanding of AD development and progression. A clearer understanding of the mechanisms underlying neurofibrillary tangle formation specifically may help to clarify the basis for dementia of AD as well as the dementias associated with other diseases that are collectively referred to as "tauopathies." |
GSE4757.qdab |
| GSE4773 |
Greene-5P01NS017771-220003 |
Parkinson's disease is a prevalent neurodegenerative disorder for which there is no cure. The cause of PD symptoms is loss of dopamine neurons in the midbrain, but it is not known why these neurons die. Pesticide exposure is epidemiologically associated with PD, and administration of the organic pesticide rotenone to rats recapitulates most of the behavioral, neurochemical, and neuropathological findings in PD, including specific death of dopamine neurons. We have developed an in vitro model of rotenone toxicity using a dopaminergic cell line (SK-N-MC neuroblastoma cells) that mimics many of the cellular changes seen with in vivo rotenone toxicity and with PD, such as alpha-synuclein aggregation and oxidative damage. We are currently using this simple model to explore mechanisms of dopaminergic neurodegeneration, with our ultimate goal being the discovery of novel mechanisms for dopaminergic neuroprotection in PD. |
GSE4773.qdab |
| GSE4817 |
Sphingosine 1-phosphate effect on glioblastoma cells in vitro |
Abstract |
GSE4817.qdab |
| GSE48350 |
Alzheimer's Disease Dataset |
This dataset contains microarray data from normal controls (aged 20-99 yrs) and Alzheimer's disease cases, from 4 brain regions: hippocampus, entorhinal cortex, superior frontal cortex, post-central gyrus. Changes in expression of synaptic and immune related genes were analyzed, investigating age-related changes and AD-related changes, and region-specific patterns of change. |
GSE48350.qdab |
| GSE48611 |
Gene expression of human isogenic trisomy 21 induced pluripotent stem cells and derived neurons |
Down syndrome (trisomy 21) is the most common genetic cause of intellectual disability, but the precise molecular mechanisms underlying impaired cognition remain unclear. Elucidation of these mechanisms has been hindered by the lack of a model system that contains full trisomy of chromosome 21 (Ts21) in a human genome that enables normal gene regulation. To overcome this limitation,we created Ts21-induced pluripotent stem cells (iPSCs) from two sets of Ts21 human fibroblasts. One of the fibroblast lines had low level mosaicism for Ts21 and yielded Ts21 iPSCs and an isogenic control that is disomic for human chromosome 21 (HSA21). Differentiation of all Ts21 iPSCs yielded similar numbers of neurons expressingmarkers characteristic of dorsal forebrain neurons that were functionally similar to controls. Expression profiling of Ts21 iPSCs and their neuronal derivatives revealed changes in HSA21 genes consistent with the presence of 50% more genetic material as well as changes in non- HSA21 genes that suggested compensatory responses to oxidative stress. Ts21 neurons displayed reduced synaptic activity, affecting excitatory and inhibitory synapses equally. Thus, Ts21 iPSCs and neurons display unique developmental defects that are consistent with cognitive deficits in individuals with Down syndrome and may enable discovery of the underlying causes of and treatments for this disorder. |
GSE48611.qdab |
| GSE48880 |
Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis |
We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone. |
GSE48880.qdab |
| GSE49845 |
miR-34 regulates JARID1A expresion (SK-N-BE2) |
p53 inactivation occurs only rarely in neuroblastoma, although miR-34, a transcriptional target of p53, is often deleted in neuroblastoma, suggesting another way in which p53 signaling might be impaired. In this study we show that miR-34 directly targets and downregulates the Polycomb Repressive Complex 2 (PRC2) and its associated histone demethylase, JARID1A, in a p53-dependent manner, |
GSE49845.qdab |
| GSE49854 |
miR-34 regulates JARID1A expresion (NB1691) |
p53 inactivation occurs only rarely in neuroblastoma, although miR-34, a transcriptional target of p53, is often deleted in neuroblastoma, suggesting another way in which p53 signaling might be impaired. In this study we show that miR-34 directly targets and downregulates the Polycomb Repressive Complex 2 (PRC2) and its associated histone demethylase, JARID1A, in a p53-dependent manner, |
GSE49854.qdab |
| GSE50161 |
Expression data from human brain tumors and human normal brain |
The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors. |
GSE50161.qdab |
| GSE50208 |
Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors |
Use existing public data, cell lines and patient tumors with a personalized medicine approach to predict effective therapies for treatment of Neurofibroma tumors. |
GSE50208.qdab |
| GSE50584 |
Expression data from human ESCs-derived neural precursors (NPs) and neurons |
We performed microarray analyses on human ESCs-derived NPs and neurons carrying loss-of-function mutation in the MeCP2 gene. |
GSE50584.qdab |
| GSE50774 |
DNA methylation alteration and gene expression sigature in brainstem, thalamic, and supratentorial gliomas |
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect due to their proximity to eloquent brain structures. Here, we performed a comprehesive genomic and epigenomic study, using gene expression and methylation microarrays, to research on th different genomic and epigenetic signatures between brainstem, thalamic, and supratentorial gliomas. |
GSE50774.qdab |
| GSE51214 |
Isolation of human iPSC-derived dopaminergic progenitors by cell sorting |
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells may inevitably contain tumorigenic or inappropriate cells. Purification of neural progenitor cells or DA neurons as suitable donor cells has been attempted, but the isolation of DA progenitor cells derived from human pluripotent stem cells has so far been unsuccessful. Here we show human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, Corin. we were able to develop a method for 1) scalable DA neuron induction on human laminin fragment and 2) sorting DA progenitor cells using an anti-Corin antibody. Furthermore, we determined the optimal timing for the cell sorting and transplantation. The grafted cells survived well and functioned as midbrain DA neurons in the 6-OHDA-lesioned rats, and showed minimal risk of tumor formation. The sorting of Corin-positive cells is favorable in terms of both safety and efficiency, and our protocol will contribute to the clinical application of human iPSCs for Parkinson’s disease. |
GSE51214.qdab |
| GSE51512 |
Gene expression profiling of BIX01294-treated human neuroblastoma cell line BE(2)-C |
Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer. |
GSE51512.qdab |
| GSE51822 |
Expression data for minimally invasive glioblastoma stem-like cell (GSC) plasma membrane markers |
We compared whole genome expression profiles of GSCs with normal human cortex, human neural stem cells (hNSC) from fetal cortex, glioblastoma (GBM) primary, and recurrent tumors to find GSC-specific plasma membrane transcripts. |
GSE51822.qdab |
| GSE51909 |
Expression data from 205432- or 206381-treated BE(2)-C cells |
Analysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with novel indole-2-carboxamide antivirals 205432 or 206381. |
GSE51909.qdab |
| GSE51978 |
Gene expression profiling in neuroblastoma cells upon CHAF1A silencing |
We used an inducible ShRNA system and microarrays to detail the global programme of gene expression underlying neuroblastoma differentiation upon CHAF1A silencing . |
GSE51978.qdab |
| GSE52127 |
Brain tumor initiating cell response to microglia |
Determination of the mechanism by which microglia regulate growth of brain tumor initiating cells (BTICs) and differentiation. Results identify the factors involved in the regulation and provide mechanistic basis. |
GSE52127.qdab |
| GSE52659 |
Expression data from WEEV infected BE(2)-C/m cells |
Analysis of transcription response of differentiated human BE(2)-C/m neuronal cells to infection with WEEV at 12 h and 24 h after infection. |
GSE52659.qdab |
| GSE53733 |
Expression data from primary Glioblastoma in adults |
Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, among the IDH1/2-wildtype patients, tumors from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. |
GSE53733.qdab |
| GSE53808 |
White Matter transcriptome in chronic alcoholism |
Chronic alcohol consumption can lead to alchohol-related brain damage (ARBD). Despite the well known acute effects of alcohol the mechanism responsible for chronic brain damage is largely unknown. Pathologically the major change is the loss of white matter while neuronal loss is mild and restricted to a few areas such as the prefrontal cortex. In order to improve our understanding of ARBD pathogenesis we used microarrays to explore the white matter transcriptome of alcoholics and controls. |
GSE53808.qdab |
| GSE5388 |
Adult postmortem brain tissue (dorsolateral prefrontal cortex) from subjects with bipolar disorder and healthy controls |
Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex) from patients with bipolar disorder and matched healthy controls. A cohort of 70 subjects was investigated and the final analysis included 30 bipolar and 31 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing. |
GSE5388.qdab |
| GSE53890 |
REST and Stress Resistance in Aging and Alzheimer’s Disease |
Comparison of the gene expression profiles of adult human brain samples from frontal cortical regions, including samples from young, middle aged, normal aged. |
GSE53890.qdab |
| GSE5389 |
Adult postmortem brain tissue (orbitofrontal cortex) from subjects with bipolar disorder and healthy controls |
Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls. Orbitofrontal cortex tissue from a cohort of 30 subjects was investigated and the final analysis included 10 bipolar and 11 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing. |
GSE5389.qdab |
| GSE5390 |
Expression profiling of human adult postmortem brain tissue from Down syndrome and healthy control subjects |
Down syndrome (DS) is the result of trisomy chromosome 21 but the mechanisms by which the genotype leads to the characteristic disease phenotype are unclear. We performed a microarray study using human adult brain tissue (dorsolateral prefrontal cortex) from DS subjects and healthy controls to characterise for the first time the human adult Down syndrome brain |
GSE5390.qdab |
| GSE54077 |
Transcriptomal Diversity of Long-Term Glioblastoma Survivors |
Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. |
GSE54077.qdab |
| GSE54565 |
Expression data from human brain anterior cingulate cortex - including control samples and samples with major depression disorders (32 samples MD1_ACC) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54565.qdab |
| GSE54566 |
Expression data from human brain amygdala - including control samples and samples with major depression disorders (28 samples MD1_AMY) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54566.qdab |
| GSE54567 |
Expression data from human brain dorsolateral prefrontal cortex - including control samples and samples with major depression disorders (28 samples BA9_M) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54567.qdab |
| GSE54568 |
Expression data from human brain dorsolateral prefrontal cortex - including control samples and samples with major depression disorders (30 samples BA9_F) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54568.qdab |
| GSE54570 |
Expression data from human brain dorsolateral prefrontal cortex - including control samples and samples with major depression disorders (26 samples NY_BA9) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54570.qdab |
| GSE54571 |
Expression data from human brain anterior cingulate cortex - including control samples and samples with major depression disorders (26 samples BA25_F) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54571.qdab |
| GSE54572 |
Expression data from human brain anterior cingulate cortex - including control samples and samples with major depression disorders (24 samples BA25_M) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54572.qdab |
| GSE54575 |
Expression data from human brain orbital ventral prefrontal cortex - including control samples and samples with major depression disorders (24 samples NY_BA47) |
Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). |
GSE54575.qdab |
| GSE56048 |
Gene profile in fetal human heart and brain |
To describe normal cardiac and brain development during late first and early second trimester in human fetuses using microarray and pathways analysis and the creation of a corresponding “normal” database. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac and brain development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15(H2) and 16-18(H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cut-off to determine differential gene expression for individual genes. Test for enrichment to identify functional groups were carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. |
GSE56048.qdab |
| GSE56906 |
Effect of EtOH on neural stem cells derived from human embryonic stem cells |
We have performed gene expression microarray analysis to profile transcriptomic signatures affected by EtOH during neural differentiation of human embryonic stem cells |
GSE56906.qdab |
| GSE58149 |
Expression analysis in hipsc-derived neurons exposed to botulinum neurotoxin A subtype 1 and a type A atoxic derivative |
Transcriptome analysis of RNA extracted from human induced pluripotent stem cell (hipsc)-derived neurons exposed to botulinum neurotoxin type A1 (BoNT/A1) and an atoxic derivative, BoNT/A ad. |
GSE58149.qdab |
| GSE59262 |
Expression data from U373 cell lines |
Intracellular progesterone receptor (PR) presents two main isoforms: PR-A and PR-B with different function and regulation. Both isoforms have been identified in astrocytomas, the most common and aggressive primary brain tumors in humans. To investigate the role of PR activity in the regulation of gene expression pattern of U373 cells, we evaluated by microarray analysis the profile of genes regulated by progesterone (10 nM), by a progesterone receptor antagonist (RU486, 10 µM) or by both steroids. |
GSE59262.qdab |
| GSE59899 |
Transient expression of CHD5 in KELLY cells |
Loss of the tumor suppressor CHD5 frequently occurs during neuroblastoma progression. |
GSE59899.qdab |
| GSE61050 |
Expression data of neural progenitor cells differentiation from human embryonic stem cells |
Mocetinostat (MGCD) which is a kind of histone deacetylase inhibitors (HDACi) promotes human embryonic stem cells (hESCs) differentiation towards neural progenitor cells (NPCs). Application of HDAC inhibitors (HDACi) increased the expression of neuroectodermal markers once neural differentiation was initiated, thereby leading to more NPC generation. |
GSE61050.qdab |
| GSE61388 |
Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain |
Caspases are cysteine-proteases with key roles in the execution phase of apoptosis. Additional cellular activities, unrelated to cell death seem to be influenced by these enzymes. Identification of genes co-regulated with caspases could help to ascertain new biological roles for these proteases.To identify genes and pathways under the influence of caspase-2 we silenced its expression in U87MG glioblastoma cell line. Transcriptional expression profiles of cells transfected with caspase-2 siRNA or control siRNA were compared. |
GSE61388.qdab |
| GSE61842 |
Defining the role of oxygen tension in human neural progenitor fate |
Hypoxia augments human embryonic stem cell self-renewal via hypoxia-inducible factor 2? (HIF2?) activated OCT4 (POU5F1) transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low oxygen (O2) tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and HIF activity instead promotes appropriate hESC differentiation. Through gain and loss of function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate towards neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types. |
GSE61842.qdab |
| GSE6451 |
A genomic screen for activators of the antioxidant response element |
The antioxidant response element (ARE) is a cis-acting regulatory enhancer element found in the 5’ flanking region of many phase II detoxification enzymes. Upregulation of ARE-dependent target genes is known to have neuroprotective effects; yet, the mechanism of activation is largely unknown. By screening an arrayed collection of approximately 15,000 full-length expression cDNAs in the human neuroblastoma cell line IMR-32 with an ARE-luciferase reporter, we have identified several cDNAs not previously associated with ARE activation. A subset of cDNAs, including sequestosome 1 (SQSTM1) and dipeptidylpeptidase III (DPP3), activated the ARE in primary mouse-derived cortical neurons. Overexpression of SQSTM1 and DPP3 in IMR-32 cells stimulated NRF2 nuclear translocation and led to increased levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), a protein which is transcriptionally regulated by the ARE. When transfected into IMR-32 neuroblastoma cells that were depleted of transcription factor NRF2 by RNA interference, SQSTM1 and DPP3 were unable to activate the ARE or induce NQO1 expression, indicating that the ARE activation upon ectopic expression of these cDNAs is mediated by NRF2. Studies with pharmacological inhibitors indicated that 1-phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) signaling are also essential for activity. Lastly, overexpression of these cDNAs conferred partial resistance to hydrogen peroxide induced toxicity, consistent with the induction of antioxidant and phase II detoxification enzymes which can protect from oxidative stress. This work and other such studies may provide mechanisms for activating the ARE in the absence of general oxidative stress, and a novel therapeutic approach to degenerative diseases and aging. |
GSE6451.qdab |
| GSE6955 |
Expression in Superior Frontal Gyrus of normal individuals or females of different ages affected by Rett syndrome |
Rett syndrome (RTT, OMIM #312750) is a severe X-linked neurodevelopmental disorder linked to heterozygous de novo mutations in the MECP2 gene. MECP2 encodes methyl-CpG-binding protein 2 (MeCP2), which represses gene transcription by binding to 5-methylcytosine residues in symmetrically positioned CpG dinucleotides. The disorder is almost exclusively diagnosed in females, because males affected by the disease usually die perinatally due to severe encephalopathy. Direct MeCP2 target genes underlying the neuropathogenesis of RTT remain largely unknown. |
GSE6955.qdab |
| GSE7142 |
Gene expression data from hypothalamic hamartomas (HH) obtained from patients with or without precocious puberty (CPP) |
Hypothalamic hamartomas (HHs) are congenital lesions of the neuroendocrine brain composed of neurons and astroglia. Frequently, HHs are associated with central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty we used cDNA arrays to compare the gene expression profile of a HH associated with CPP with three HHs not accompanied by sexual precocity. Our aim was to identify genes whose expression may be selectively altered in the HH with CPP and hence, involved in the onset of puberty. |
GSE7142.qdab |
| GSE7178 |
Comparison of gene expression data between wild-type and DM1-affected Neural Precursors Cells (NPC) |
Analysis of genes that were differentially expressed in mutant VUB03_DM1 as compared to controls VUB01 and SA01 Neural Precursor cells |
GSE7178.qdab |
| GSE7179 |
Comparison of gene expression data between wild-type and DM1-affected undifferentiated hES cells. |
Analysis of genes that were differentially expressed in mutant VUB03_DM1 as compared to controls VUB01 and SA01 undifferentiated hES cells |
GSE7179.qdab |
| GSE7181 |
CD133+ and CD133- CSC lines in primary human GBM |
We cultured tumor cells from 22 GBM under medium conditions favoring the growth of neural stem cells. 11 out of 15 primary GBM contained a significant CD133+ subpopulation that comprised cells showing all hallmarks of neural stem cells. Cell lines derived from these CD133+ GBM showed a neurosphere-like, non-adherent growth pattern. In contrast, 4 out of 15 cell lines derived from primary GBM grew adherent in vitro and were driven by CD133- tumor cells that fulfilled stem cell criteria. In vivo, these GBM were characterized by a significantly lower proliferation index but similar GFAP staining as compared to CD133+ GBM. Gene arrays from 2x3 representative cells lines are given. |
GSE7181.qdab |
| GSE7529 |
Supplementary Table 3. Validation of microarray data by RT-PCR. Comparison between Affymetrix fold-change and Real-Time PCR fold-change for single gene header descriptions |
Tumor tissue heterogeneity is a well known feature of several solid tumors. Neuroblastic Tumors (NTs) is a group of paediatric cancers with a great tissue heterogeneity. Most of NTs are composed of undifferentiated, poorly differentiated or differentiating neuroblastic (Nb) cells with very few or absent Schwannian stromal (SS) cells: these tumors are grouped as Neuroblastoma (Schwannian stroma-poor). The remaining NTs are composed of abundant SS cells and classified as Ganglioneuroblastoma (Schwannian stroma-rich) intermixed or nodular and Ganglioneuroma. The importance to understand Nb and SS gene signatures in NTs, is to clarify the complex network mechanism of tumor growth and progression. In order to identify the Nb and SS cells gene signatures, we analyzed the gene expression profiling of 19 cases of neuroblastic tumors: 10 stroma poor (NTs-SP) and 9 stroma rich (NTs-SR), by high density oligonucleotide microarrays. Moreover, the analysis was performed in parallel on both whole and laser microdissected tumor samples: from 4 of 19 cases, was isolated different areas all composed of pure cellular populations. |
GSE7529.qdab |
| GSE7540 |
Gene expression analysis of the human and chimpanzee brain |
The origin of humans was accompanied by the emergence of new behavioral and cognitive functions, including language and specialized forms of abstract representation. However, the molecular foundations of these human capabilities are poorly understood. Because of the extensive similarity between human and chimpanzee DNA sequences, it has been suggested that many of the key phenotypic differences between species result primarily from alterations in the regulation of genes rather than in their sequences. |
GSE7540.qdab |
| GSE7621 |
Expression data of substantia nigra from postmortem human brain of Parkinson's disease patients (PD) |
We used microarrays to detail the global program of gene expression underlying Parkinson's disease |
GSE7621.qdab |
| GSE7696 |
Glioblastoma from a homogenous cohort of patients treated within clinical trial |
Analysis of 80 glioblastoma specimen of patients treated within clinical trials and 4 samples of "normal" brain tissue (non-tumoral). The data was used to identify factors of resistance to a chemoradiation therapy protocol of radiotherapy and concomitant and adjuvant temozolomide (alkylating agent). |
GSE7696.qdab |
| GSE8049 |
Expression analyses of glioblastoma derived neurosphere cultures |
Recent studies demonstrated that tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We established glioblastoma stem-like (GS-) cell cultures from 9 different glioblastomas, 8 of which generated stably expandable cell lines. Analyzing GS-cell cultures, we discovered two clearly discernable phenotypes. |
GSE8049.qdab |
| GSE8353 |
A Mathematical Model for Affymetrix GeneChip Probe Level Data |
Affymetrix GeneChip PM-MM probe pair is designed with the intension of measuring non-specific binding. Though the rationale behind the design id that a PM probe is expected to have a larger value than that of the MM probe, there are many exceptions in actual data. We gave an explanation for this inconsistency based on the assumption of functional states of a gene ‘ON/OFF’. Our hypothesis on PM-MM probe pairs is that the logarithmic of PM and MM values have the same distribution when gene is in OFF state. It means that the probability of MM > PM is expected to be equal to that of MM < PM for OFF genes. The validity of the hypothesis was given by inter-platform comparisons using common targets among three different types of platforms. |
GSE8353.qdab |
| GSE8397 |
Expression profiling of the Parkinsonian Brain |
Affymetrix HG_U133 array sets (A and B chips) were used to determine the whole genome transcription profile of clinically documented and neuropathologically confirmed cases of sporadic Parkinson's disease as well as controls. |
GSE8397.qdab |
| GSE8692 |
Endogeneous mRNA level fluctuations in various brain tumor cells |
Background: microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of the miRNA to a target mRNA, usually in its 3’ untranslated region (UTR). As a result, translation of the target mRNA is inhibited and sometimes the mRNA itself can be de-stabilized. The inhibitory effects of miRNAs have been linked to many diverse cellular processes including malignant proliferation and apoptosis, development and differentiation, metabolic processes and neural plasticity. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. |
GSE8692.qdab |
| GSE9169 |
Gene expression during neuronal differentiation in two subtypes of SH-SY5Y |
Background: SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA), but the molecular mechanism of activation in the signaling pathway mediated by phosphatidylinositol 3-kinase (PI3K) is not sufficiently understood. To shed new light on the mechanism, we comprehensively compared the gene expression profiles between SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E), each of which showed a different phenotype during RA-mediated differentiation. Results: SH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor (BDNF) for full differentiation. In combination with perturbation using a PI3K inhibitor, LY294002, we identified 386 genes and categorized them into two clusters dependent on the PI3K signaling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster was greatly reduced in SK-N-SH cells or partially impaired in SH-SY5Y-E cells in coincidence with a defect in the neuronal phenotype of these cell lines. Additional stimulation with BDNF induced a set of neural genes which were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in the differentiated SH-SY5Y-A cells. Conclusions: We identified the gene clusters controlled by PI3K- and TRKB-mediated signaling pathways during differentiation in two subtypes of SH-SY5Y cells. TRKB-mediated bypass pathway compensates for the impaired neural functions generated by defects in several signaling pathways including PI3K in SH-SY5Y-E cells. The expression profiling data are useful for further studies to elucidate the signal transduction-transcriptional network including PI3K and/or TRKB. |
GSE9169.qdab |
| GSE9335 |
Genome-wide analyses of human perisylvian cerebral cortical patterning |
Despite the well-established role of the frontal and posterior peri-sylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in human brain. We performed a genome-wide analysis of human cerebral patterning during mid-gestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed (DE) between superior temporal gyrus (STG) and the remaining cerebral cortex (CTX). GO categories representing transcription factors were enriched in STG, while cell-adhesion and extracellular matrix molecules, were enriched in the other cortical regions. Q-PCR or in situ hybridization were performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LMO4), a gene known to be involved in the asymmetric pattering of the peri-sylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin Associated Protein-Like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy and language delay, showed a remarkable pattern of anterior enriched expression in cortical regions important for human higher cognition. Importantly, a similar pattern was not observed in the mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and disorders that disrupt them. |
GSE9335.qdab |
| GSE9770 |
Non-demented individuals with intermediate Alzheimer's neuropathologies - neuronal expression (6 regions) |
Layer II stellate neurons (entorhinal cortex) and layer III cortical neurons (hippocampus CA1, middle temporal gyrus, posterior cingulate, superior frontal gyrus, primary visual cortex) were gene expression profiled. Brain regions are from non-demented individuals with intermediate Alzheimer's disease neuropathologies |
GSE9770.qdab |
| GSE9807 |
Expression data from RNAi SNCA treated human neuroblastoma cell line |
The pre-synaptic protein ?-synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of ?-synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of ?-synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of ?-synuclein by RNA interference. |
GSE9807.qdab |
| GSE9835 |
Gene Expression Changes in Response to Baculoviral Vector Transduction of Neuronal Cells In Vitro |
Recombinant baculoviral vectors efficiently transduce several types of cells in the brain. To characterize host responses to viral challenge, thus verifying the suitability of using the virus for the development of gene therapy strategies in the central nervous system, we used cDNA microarray technology to examine in vitro and in vivo global cellular gene expression profiles after viral transduction. We demonstrated that the transduction induced host antiviral responses as a major reaction in all three types of samples profiled, including the rat brain, cultured human astrocytes and human neuronal cells. The related genes were mainly those associated with innate immunity. Several genes of the major histocompatibility complex molecules, an important component of the host adaptive immunity to exogenous pathogens, were up-regulated in the rat brain and human astrocytes, but not in neuronal cells. We also observed that genes related to cell death and apoptosis were up-regulated and genes related cell cycle regulation were down-regulated in neuronal cells, but not obviously affected in astrocytes. These findings should be useful in understating the molecular basis for neural cell response to baculoviral transduction and guiding rational applications of baculoviral vectors in the central nervous systems |
GSE9835.qdab |
| GSE9861 |
Effect of Plasmodium falciparum infected erythrocytes on primary human brain microvascular endothelial cell |
Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparum–infected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor B (NF-B) activation cascade. The proinflammatory NF-B pathway was central to the regulation of the P falciparum–modulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparum–infected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria. |
GSE9861.qdab |
| GSE9939 |
Gene expression data on human optic nerve head astrocytes in normal Caucasian and African americans |
To determine whether optic nerve head astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary culture of astrocytes from normal African American donors, compared to astrocytes from normal Caucasian American donors. All donors have no histories of eye disease, diabetes, or chronic CNS disease. |
GSE9939.qdab |
| GSE9940 |
ES cells, EBs grown in suspension (d6), PEL (d10) stage and neural rosettes (d17) (zhang-affy-human-346640) |
Human embryonic stem cells not only provide a continuous cell source for potential cell therapy but also offer a system to unveil events of embryonic development in humans. This proposal will examine how the earliest neural cells, neuroepithelia, are specified from the naïve ES cells, and test the hypothesis that neural specification in humans employs a similar mechanism as in other vertebrates. We will first re-create in culture the developmental events of the first 2-3 weeks of human embryonic development during which ES cells will be differentiated through the stages of embryoid bodies, primitive ectoderm cells, neural tube-like rosette cells. The stage-specific events will be defined by DNA microarray analysis along with the characteristic morphologic changes. This study will lead to an optimized procedure for generating enriched neural precursor cells, which will lay the groundwork for potential use of human ES cells in the treatment of neurological injuries and diseases. |
GSE9940.qdab |
| GSE9963 |
Gene expression data on human optic nerve head astrocytes |
This SuperSeries is composed of the SubSeries listed below. |
GSE9963.qdab |
| gsea_mir |
gsea_mir |
GSEA MIR |
gsea_mir.qdab |
| gsea_cgp |
gsea_cgp |
GSEA CGP |
gsea_cgp.qdab |
| mint |
mint |
MINT |
mint.qdab |
| mips |
mips |
MIPS |
mips.qdab |
| intact |
intact |
IntAct |
intact.qdab |
| biogrid |
biogrid |
BioGRID |
biogrid.qdab |
| jaspar_human |
jaspar_human |
Jasper |
jaspar_human.qdab |
| microcosm |
microcosm |
microcosm |
microcosm.qdab |