Distinct roles of SOX9 in self-renewal of progenitors and mesenchymal transition of the endothelium [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1040200 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26825390.fastq.gz | Fastqsanger.gz | |||
| SRR26825391.fastq.gz | Fastqsanger.gz | |||
| SRR26825392.fastq.gz | Fastqsanger.gz | |||
| SRR26825393.fastq.gz | Fastqsanger.gz | |||
| SRR26825394.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Regenerative capabilities of the human endothelium are governed by vessel-resident progenitors termed endothelial colony forming cells (ECFCs). Endothelial cells acquire mesenchymal phenotypes during atherogenesis, via a process termed endothelial-to-mesenchymal transition (EndMT). This study aimed to investigate the molecular drivers of EndMT in the progenitor population under an atherogenic model. In the presence of oxidised low-density lipoprotein (oxLDL), cultured human ECFCs displayed classical features of EndMT, through reduced endothelial gene and protein expression, function as well as increased mesenchymal genes, contractility, and motility. Importantly, in vitro oxLDL resulted in a dramatic loss in progenitor self-renewal through single-cell colony formation assay and numbers. RNA sequencing of ECFCs exposed or not to oxLDL validated gene expression changes suggesting EndMT but identified SOX9 as one of the highly differentially expressed genes. ATACseq revealed SOX9 binding sites were associated with regions of dynamic chromosome accessibility resulting from exposure to oxLDL. EndMT phenotype and gene expression changes induced by oxLDL in vitro or high fat diet (HFD) in vivo was reversed by an shRNA knockdown of SOX9 or endothelial specific conditional knockout of Sox9 in murine models respectively. Finally, analysis of single cell RNA sequencing of human atherosclerotic aorta identified endothelial populations with mesenchymal characteristics overexpressing SOX9 when compared to controls. Overall, our findings support that in the atherogenic process, EndMT induced by oxLDL or HFD is driven by SOX9 and strongly affects progenitor function opening new avenues for targeting this process.
2024-08-30 | GSE247711 | GEO
Project description:Regenerative capabilities of the human endothelium are governed by vessel-resident progenitors termed endothelial colony forming cells (ECFCs). Endothelial cells acquire mesenchymal phenotypes during atherogenesis, via a process termed endothelial-to-mesenchymal transition (EndMT). This study aimed to investigate the molecular drivers of EndMT in the progenitor population under an atherogenic model. In the presence of oxidised low-density lipoprotein (oxLDL), cultured human ECFCs displayed classical features of EndMT, through reduced endothelial gene and protein expression, function as well as increased mesenchymal genes, contractility, and motility. Importantly, in vitro oxLDL resulted in a dramatic loss in progenitor self-renewal through single-cell colony formation assay and numbers. RNA sequencing of ECFCs exposed or not to oxLDL validated gene expression changes suggesting EndMT but identified SOX9 as one of the highly differentially expressed genes. ATACseq revealed SOX9 binding sites were associated with regions of dynamic chromosome accessibility resulting from exposure to oxLDL. EndMT phenotype and gene expression changes induced by oxLDL in vitro or high fat diet (HFD) in vivo was reversed by an shRNA knockdown of SOX9 or endothelial specific conditional knockout of Sox9 in murine models respectively. Finally, analysis of single cell RNA sequencing of human atherosclerotic aorta identified endothelial populations with mesenchymal characteristics overexpressing SOX9 when compared to controls. Overall, our findings support that in the atherogenic process, EndMT induced by oxLDL or HFD is driven by SOX9 and strongly affects progenitor function opening new avenues for targeting this process.
2024-08-30 | GSE247709 | GEO
Project description:Distinct roles of SOX9 in self-renewal of progenitors and mesenchymal transition of the endothelium
| PRJNA1040198 | ENA
Project description:Distinct roles of SOX9 in self-renewal of progenitors and mesenchymal transition of the endothelium [ATAC-seq]
| PRJNA1040199 | ENA
Project description:Regenerative capabilities of the endothelium rely on vessel-resident progenitors termed endothelial colony forming cells (ECFCs). This study aimed to investigate if these progenitors are impacted by conditions (i.e., obesity or atherosclerosis) characterized by increased serum levels of oxidized low-density lipoprotein (oxLDL), a known inducer of Endothelial-to-Mesenchymal Transition (EndMT). Our investigation focused on understanding the effects of EndMT on the self-renewal capabilities of progenitors and the associated molecular alterations. In the presence of oxLDL, ECFCs displayed classical features of EndMT, through reduced endothelial gene and protein expression, function as well as increased mesenchymal genes, contractility, and motility. Additionally, ECFCs displayed a dramatic loss in self-renewal capacity in the presence of oxLDL. RNA-sequencing analysis of ECFCs exposed to oxLDL validated gene expression changes suggesting EndMT and identified SOX9 as one of the highly differentially expressed genes. ATAC sequencing analysis identified SOX9 binding sites associated with regions of dynamic chromosome accessibility resulting from oxLDL exposure, further pointing to its importance. EndMT phenotype and gene expression changes induced by oxLDL in vitro or high fat diet (HFD) in vivo were reversed by the silencing of SOX9 in ECFCs or the endothelial-specific conditional knockout of Sox9 in murine models. Overall, our findings support that EndMT affects vessel-resident endothelial progenitor's self-renewal. SOX9 activation is an early transcriptional event that drives the mesenchymal transition of endothelial progenitor cells. The identification of the molecular network driving EndMT in vessel-resident endothelial progenitors presents a new avenue in understanding and preventing a range of condition where this process is involved.
| S-EPMC11303482 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-30 | GSE247712 | GEO
Project description:Cell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines. Asymmetric self-renewal occurs when murine embryo fibroblasts that are otherwise p53-null are induced to express physiological levels of wildtype p53 protein (Asym). To distinguish p53-responsive genes that also require induction of asymmetric self renewal (i.e., ASRA genes) and/or non-random sister chromatid segregation for change, an additional control cell line, which continues to symmetrically self-renew (with random sister chromatid segregation) even when p53 is induced, was also compared (Symp53). This congenic cell line constitutively expresses the type II inosine monophosphate dehydrogenase (IMPDH II; the rate-limiting enzmye for guanine ribonucleotide biosynthesis) and, thereby, prevents p53-induced asymmetric self-renewal and non-random sister chromatid segregation. Three biological replicates of asymmetrically self-renewing cultures (Asym1-3) were compared with cultures that were symmetrically self-renewing - either because they did not express p53 (3 biological replicates, Sym1-3) or they expressed constitutive IMPDH II (i.e., not regulated by p53) as well as p53 (2 biological replicates, Symp53_1 and 2.)
2010-12-22 | E-GEOD-25334 | biostudies-arrayexpress
Project description:Cell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines. Asymmetric self-renewal occurs when murine embryo fibroblasts that are otherwise p53-null are induced to express physiological levels of wildtype p53 protein (Asym). To distinguish p53-responsive genes that also require induction of asymmetric self renewal (i.e., ASRA genes) and/or non-random sister chromatid segregation for change, an additional control cell line, which continues to symmetrically self-renew (with random sister chromatid segregation) even when p53 is induced, was also compared (Symp53). This congenic cell line constitutively expresses the type II inosine monophosphate dehydrogenase (IMPDH II; the rate-limiting enzmye for guanine ribonucleotide biosynthesis) and, thereby, prevents p53-induced asymmetric self-renewal and non-random sister chromatid segregation.
2010-12-22 | GSE25334 | GEO
Project description:Sox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/β-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion. Sox9 ChIP-seq analysis in K14CreER SmoM2 cells.
2015-05-13 | E-GEOD-68755 | biostudies-arrayexpress
Project description:Sox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/β-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
2015-05-13 | GSE68613 | GEO