Determination of Sox10-regulated genes in the oligodendroglial precursor cell line OLN93
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ABSTRACT:
PROVIDER: PRJNA562933 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10037356.fastq.gz | Fastqsanger.gz | |||
| SRR10037357.fastq.gz | Fastqsanger.gz | |||
| SRR10037358.fastq.gz | Fastqsanger.gz | |||
| SRR10037359.fastq.gz | Fastqsanger.gz |
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Project description:To determine Sox10-regulated genes in the oligodendroglial precursor cell line OLN93, CRISPR/Cas9-mediated genome editing was performed to inactivate Sox10. For CRISPR/Cas9-mediated Sox10 inactivation, two guide sequences (5’-GCTGCGAGCCAGCCCAGGGCC-3’ for clone A and 5’-GTTGCCCAATTCGCCG GGCCC-3’ for clone B) were separately cloned into pX330. Oln93 cells were co-transfected with pEGFP-N1 and the pX330 plasmids that express the respective guide RNA and SpCas9. Transfected GFP-positive cells were enriched by fluorescence activated cell-sorting and seeded at single cell density in 96-well plates. Homogeneously GFP-expressing clones were analysed for loss of Sox10 protein by immunocytochemistry. Clones without Sox10 protein were obtained with both guide RNAs. Sox10 inactivation was confirmed by Sanger sequencing of the Sox10 gene. RNA was isolated from one clone A and one clone B as well as two independent RNA samples of wildtype OLN93 cells and submitted to RNA-seq.
2019-12-15 | GSE136659 | GEO
Project description:Oligodendroglial cells are responsible for the generation of myelin sheaths in the central nervous system and thereby render rapid saltatory conduction possible. During development, oligodendroglial cells express the three paralogous transcription factors Sox8, Sox9 and Sox10. In mature oligodendrocytes Sox8 and Sox10 expression persists. Whereas Sox9 and Sox10 fulfill important regulatory roles in these cells, Sox8 has only a limited impact on oligodendroglial development and myelination. By replacing Sox10 with Sox8 or Sox9 in the oligodendroglial Oln93 cell line and by comparing expression profiles, we show that Sox8 regulates the same processes as Sox10 and Sox9, but has a substantially lower transcriptional activity under standard culture conditions.
2025-01-02 | GSE280389 | GEO
Project description:To gain insight of how ErbB signaling in oligodendroglial progenitor cell to newly-formed oligodendrocyte stages (OPC-NFOs) regulated adolescent oligodendroglial development, we did RNA-seq analyses of subcortical white matter tissues isolated from Sox10-ErbB2V664E mice or Sox10-dnEGFR mice and their littermate controls after doxycycline treatment, respectively. Both mice were revealed hypomyelination although OPC proliferation or survival were differently altered in them. For each group we sequenced three pairs of samples, and revealed 2298 genes that had altered expression in the white matter of Sox10-ErbB2V664E mice, as well as 1184 genes that had altered expression in that of Sox10-dnEGFR mice. By comparing the two groups of genes, we identified 50 genes which had opposite expression tendency in the two mouse lines which was potentially involved in ErbB signaling and contributed to regulation of OPC proliferation and survival. Meanwhile, we identified 68 genes which exhibited similar expression tendency in Sox10-ErbB2V664E and Sox10-dnEGFR mice which had potential in the regulation of central myelination.
2018-12-08 | GSE123491 | GEO
Project description:Molecular cause of the differential activity of Sox8 and Sox10 in oligodendroglial cells
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Project description:The transcription factor SRY(sex related protein-Y)-box10 (SOX10) plays a key role in the development of melanocytes and peripheral glial cells from neural crest precursors. Recently, we and other groups found SOX10 to be involved in melanoma initiation, proliferation, invasion, and survival. However, specific mediators which impart the oncogenic role of SOX10 in melanoma remain widely unknown. To identify potential target genes of SOX10, we performed RNA sequencing to analyze genome-wide expression alterations after ectopic expression of SOX10. Among nine genes differentially regulated by SOX10, only peripheral myelin protein 2 (PMP2) was found upregulated in several other melanoma cell lines. PMP2 is one of the most abundant myelin proteins in glial cells and is necessary for the formation and maintenance of the myelin sheath. We detected PMP2 expression in a subset of human melanoma cell lines while it was absent in human melanocytes and fibroblasts. Direct binding of SOX10 to the PMP2 promoter was shown by chromatin immunoprecipitation and electrophoretic shift assay. In three-dimensional spheroid assays, we found that PMP2 overexpression increased melanoma cell invasion. In conclusion, we identified PMP2 as target gene of SOX10 and propose a novel role for PMP2 in melanoma cell invasion.
2017-12-31 | GSE79988 | GEO
Project description:We report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to convert mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures that resemble OPCs.
2013-04-07 | GSE40421 | GEO
Project description:The MITF and SOX10 transcription factors regulate the expression of genes important for melanoma proliferation, invasion and metastasis. Despite growing evidence of the contribution of long non-coding RNAs (lncRNAs) in melanoma and other cancers, their functions within MITF-SOX10 transcriptional programmes is poorly investigated. Here, we identify 245 candidate melanoma associated lncRNAs whose loci are co-occupied by MITF-SOX10 and are enriched at active enhancer-like regions. We characterise the function and molecular mechanism of action of one of these lncRNAs, Disrupted In Renal Carcinoma 3 (DIRC3), and show that it operates as a MITF-SOX10 regulated tumour suppressor. DIRC3 depletion in human melanoma cells leads to increased anchorage-independent growth, a hallmark of malignant transformation, whilst melanoma patients classified by low DIRC3 expression have decreased survival. DIRC3 is a nuclear lncRNA that functions locally to activate expression of its neighbouring IGFBP5 tumour suppressor through modulation of chromatin structure and suppression of SOX10 binding to putative regulatory elements within the DIRC3 locus. In turn, DIRC3 dependent regulation of IGFBP5 impacts the expression of genes important for cell metabolism, oxidative phosphorylation and cancer. Our work indicates that lncRNA components of MITF-SOX10 networks are an important new class of melanoma regulators and candidate therapeutic targets.
2019-11-11 | GSE129078 | GEO
Project description:Multiple sclerosis (MS) is the most frequent demyelinating disease and despite significant advances in the immunotherapy, disease progression still cannot be prevented. Promotion of remyelination, an endogenous repair process, represents a promising new treatment approach. However, spontaneous remyelination frequently fails in MS lesions due to an impaired differentiation of progenitor cells into mature, myelinating oligodendrocytes. Intrinsic oligodendroglial and extrinsic inflammatory factors may contribute to this differentiation block. Therefore, we compared induced pluripotent stem cell (iPSC)-derived oligodendrocytes (hiOL) from MS patients and healthy controls as well as their response to extrinsic factors. While functional capabilities or proteome compostion of both cell types were virtually indistinguishable, we discovered that Interferon-gamma (IFNγ) producing immune cells significantly impaired oligodendroglial differentiation and observed no differences in the functional capabilities or the proteome. In summary, these data indicate that the oligodendroglial differentiation block is not due to intrinsic oligodendroglial factors, but rather caused by the inflammatory environment present in MS lesions. These findings may contribute to the development of remyelination promoting strategies in MS.
2020-09-04 | PXD016043 | Pride
Project description:We performed ChIP-Seq analysis of SOX10, histone H3 lysine 27 acetylation (H3K27ac) and H3K27 trimethylation (H3K27me3) in melanocytes to profile the genomic binding sites of SOX10 and the chromatin landscape. In parallel, we generated Sox10 haploinsufficient cell lines using gene knockout approaches and conducted microarray gene expression analysis to identify functional gene targets of SOX10 transcriptional regulation in melanocytes. We demonstrate that SOX10 predominantly engages “open” chromatin, binds to melanocyte enhancer elements and plays a central role in transcriptional activation and repression of functionally distinct classes of genes. Furthermore, we identified cis-regulatory sequence motifs of putative co-regulatory transcription factors that define SOX10-activated and SOX10-repressed target genes. Our results uncover novel mechanisms and roles of SOX10 in global transcriptional regulation of diverse regulatory pathways in the melanocyte lineage. These results indicated that SOX10 plays a role in activation and repression of distinct classes of genes. Microarray gene expression analysis in Sox10 haploinsufficient immortal melanocyte cell lines derived from 3-day-old Sox10LacZ/+; Ink4a-Arf null mice. Syngeneic control cells were melan-Ink4a-Arf-1.
2015-07-03 | E-GEOD-69860 | biostudies-arrayexpress
Project description:Given the heterogeneous expression of SOX10 in naïve melanoma, we sought to characterize SOX10 deficient population. To this end, we generated SOX10 CRISPR/Cas9 knockouts using two different guide RNAs (gRNA, #2 and #4) in the A375 (BRAF mutant) metastatic cell line. Using this approach, we identified multiple clones with loss of SOX10 expression. RNA-seq was performed to characterize the SOX10-regulated transcriptome. We used GSEA analysis to evaluate significant pathway changes in SOX10 knockout cells when compared to parental cells. We observed an enrichment in pathways associated with the tumor microenvironment (epithelial-mesenchymal transition; TGF beta signaling; extracellular structure organization; apical junction; hypoxia; angiogenesis), alterations in metabolic pathways (increase in the glycolysis pathway), a reduction in MYC and E2F targets and upregulation in p53 pathway and TNFA signaling via NFkB in the SOX10 knockout cells compared to parental cells. SOX10 negative clones have been identified in the minimal residual disease in BRAF mutant PDX models following BRAF and MEK inhibition and in patient samples while on treatment and SOX10 loss has been described as a resistant mechanism in BRAF mutant melanoma patients following vemurafenib treatment. Thus, we also analyzed the transcriptome profile of SOX10 low/deficient cells that arose following BRAFi+MEKi treatment in vivo. We performed GSEA analysis on RNA-seq data of CRT34 and CRT35 cells compared to parental A375 cells. CRT34 and CRT35 showed a very similar transcriptome profile to SOX10 KO cells when compared to A375 parental cells
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