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GSE19403
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that 50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedbut not normaladult white matter. We report that -catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of -catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.
Publication Title
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development.
Publication Title
Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Solid tumors are less oxygenated than normal tissues, and for this reason the cancer cells have developed several molecular mechanisms of adaptation to hypoxic environment. Moreover, his poor oxygenation is a major indicator of an adverse prognosis and leads resistance to standard anticancer treatment. Previous reports from this laboratory showed an involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions, and on the basis of these observations, we hypothesized that Che-1 might have a role in the response of cancer cells to hypoxia. Methods: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA, was subjected to normoxic and hypoxic conditions to perform studies about the role of this protein in metabolic adaptation and cell proliferation. The expression of Che-1 under normoxia or hypoxia was detected using western blot assays; cell metabolism was assessed by NMR spectroscopy and functional assays. Further molecular studies were performed by RNA seq, qRT-PCR and ChIP analysis. Results: In this paper we report that Che-1 expression is required for the adaptation of the cells to hypoxia, playing and important role in metabolic modulation. Indeed, Che-1 depletion impacted on glycolysis by altering the expression of several genes involved in the response to hypoxia by modulating the levels of HIF-1alpha. Conclusions: These data demonstrate a novel player in the regulation of a HIF1alpha in response to hypoxia. We found that the transcriptional down-regulation of a members of E3 ubiquitin ligase family SIAH2 by Che-1, produces a failure in the degradation by the hydroxylase PHD3 with a decrease in HIF-1alpha levels during hypoxia. Overall design: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA was profiled for mRNA high-troughput sequencing (RNA-seq)
Publication Title
Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer
Description
Digital gene expression profiling was used to invesigate the differetiated genes between primary mouse hepatic stellate cells infected with AGGF1 adenovirus particles or negative control adenovirus pairticles. Overall design: Primary hepatic stellate cells isolated from mice were cultured in vitro, infected with AGGF1 adenovirus particles or negative control adenovirus particles, at day 8, total RNA were prepared and used for digital gene expression tag profiling.
Publication Title
Angiogenic factor with G patch and FHA domains 1 (Aggf1) regulates liver fibrosis by modulating TGF-β signaling.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Che-1 is a RNA Polymerase II binding protein involved in the regulation of gene transcription. We have observed that Che-1 depletion induces apoptosis in several cancer cells expressing mutated forms of p53. We used microarrays to investigate classes of genes regulated by Che-1 in one of these cell lines.
Publication Title
Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
To find regulated genes during peak inflammation of rheumatoid arthritis (RA), we have collected synovium from mouse Serum Transfer Arthtitis (STA) model at day 0 (Non Arthritic) and day 10 (Peak Inflammation).
Publication Title
Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- IlluminaHiSeq2000
Description
Ribosome profiling of MDA-MB-231 cells treated with Silvestrol to monitor transcriptome wide, eIF4A-dependent changes in translation efficiency Overall design: Translation efficiency (TE) of mRNAs dervied from ribosome footprints was monitored in the presence or absence of 25 nM Silvestrol, an inhibitor of eukaryotic translation initiation factor 4A (eIF4A). Transcripts with reduced TE in the presence of Silvestrol were compare to transcripts with reduced TE in the presence of INK128, a catalytic mTOR inhbitor.
Publication Title
Transcriptome-wide characterization of the eIF4A signature highlights plasticity in translation regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The growth and fruit quality of grapevine are widely affected by abnormal climatic conditions such as water deficit. But how grapevine responds to drought stress is still largely unknown. Here we found that VaNAC26, a member of NAC transcription factor family, was up-regulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardiness wild Vitis species. Ectopic overexpression of VaNAC26 enhanced the drought and salt tolerances in transgenic Arabidopsis. Higher activities of antioxidant enzymes and the lower concentration of H2O2 and O2- were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicate that the reactive oxygen species (ROS) scavenging was enhanced by VaNAC26 in transgenic lines. Microarray based transcriptome analysis reveals that genes related to jasmonic acid (JA) synthesis and signaling were up-regulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on NACRS motif, which was broadly existent in the promoter regions of up-regulated genes in transgenic lines. Endogenous JA content was found increased obviously in VaNAC26-OE-2/3 lines. Our data suggests that VaNAC26 responds to abiotic stresses and may enhance the drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.
Publication Title
Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We generated gene expression profiles of 5 time points in murine lung development (E11.5, E13.5, E14.5, E16.5 and P5). The goal of this study was to establish a reference data set for exploration of large-scale similarities between transcriptomes in development and cancer.
Publication Title
Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers.
Sample Metadata Fields
No sample metadata fields
View Samples