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Homo sapiens
86 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
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.
Publication Title
Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y.
Sample Metadata Fields
Cell line
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GSE67458- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Myocyte enhancer factor 2B (MEF2B) is a transcription factor with somatic mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The recurrence of these mutations indicates that they may drive lymphoma development. However, inferring the mechanisms by which they may drive lymphoma development was complicated by our limited understanding of MEF2Bs normal functions. To expand our understanding of the cellular activities of wildtype (WT) and mutant MEF2B, I developed and addressed two hypotheses: (1) identifying genes regulated by WT MEF2B will allow identification of cellular phenotypes affected by MEF2B activity and (2) contrasting the DNA binding sites, effects on gene expression and effects on cellular phenotypes of mutant and WT MEF2B will help refine hypotheses about how MEF2B mutations may contribute to lymphoma development. To address these hypotheses, I first identified genome-wide WT MEF2B binding sites and transcriptome-wide gene expression changes mediated by WT MEF2B. Using these data I identified and validated novel MEF2B target genes. I found that target genes of MEF2B included the cancer genes MYC, TGFB1, CARD11, NDRG1, RHOB, BCL2 and JUN. Identification of target genes led to findings that WT MEF2B promotes expression of mesenchymal markers, promotes HEK293A cell migration, and inhibits DLBCL cell chemotaxis. I then investigated how K4E, Y69H and D83V mutations change MEF2Bs activity. I found that K4E, Y69H and D83V mutations decreased MEF2B DNA binding and decreased MEF2Bs capacity to promote gene expression in both HEK293A and DLBCL cells. These mutations also reduced MEF2Bs capacity to alter HEK293A and DLBCL cell movement. From these data, I hypothesize that MEF2B mutations may promote DLBCL and FL development by reducing expression of MEF2B target genes that would otherwise function to help confine germinal centre B-cells to germinal centres. Overall, my research demonstrates how observations from genome-scale data can be used to identify cellular effects of candidate driver mutations. Moreover, my work provides a unique resource for exploring the role of MEF2B in cell biology: I map for the first time the MEF2B regulome, demonstrating connections between a relatively understudied transcription factor and genes significant to oncogenesis.
Publication Title
MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line, Race
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We performed tiling array experiments to examine whole genome expression in human tissues. We investigated tissue specificity and association between evolutionary sequence conservation and transcription.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line, Race
View Samples- Mus musculus
- 103 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The adult mammalian brain is composed of distinct regions that have specialized roles. The BF/POA regions are thought to have an important role in the regulation of sleep/wake behavior. However, genetic markers of the responsible cells for the regulation of sleep/wake behavior are largely unknown. To identify the molecular markers of the BF/POA regions, we sampled the BF/POA regions and compared gene expression in the BF/POA regions with those of other brain regions which we previously reported in the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 102 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The adult mammalian brain is composed of distinct regions that have specialized roles. To dissect molecularly this complex structure, we conducted a project, named the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding. To avoid confusion from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the sample sets for DNA-microarray assays. Therefore, we focused only on spatial differences in gene expression. We then used informatics to identify candidates for (1) genes with high or low expression in specific regions, (2) switch-like genes with bimodal or multimodal expression patterns, and (3) genes with a uni-modal expression pattern that exhibit stable or variable levels of expression across brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 102 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
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.
Publication Title
Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 70 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development, it has been difficult to determine how neural progenitor cells are heterogeneous, due to their dynamic changes in nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage.
Publication Title
Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 68 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During cerebral development, a variety of neurons are sequentially generated by self-renewing progenitor cells, apical progenitors (APs). A temporal change in AP identity is thought to produce a diversity of progeny neurons, while underlying mechanisms are largely unknown. Here we performed single cell genome-wide transcriptome profiling of APs at different neurogenic stages, and identified a set of genes that are temporally expressed in APs in a manner independent of differentiation state. Surprisingly, the temporal pattern of such AP gene expression was not affected by arresting cell cycling. Consistently, a transient cell cycle arrest of APs in vivo did not prevent descendant neurons to acquire their correct laminar fates. in vitro cell culture of APs revealed that transitions in AP gene expression involved in both cell-autonomous and non-autonomous mechanisms. These results suggest that timers controlling AP temporal identity run independently of cell cycle progression and Notch activation mode.
Publication Title
Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells.
Sample Metadata Fields
Specimen part
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