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ETV2 Overexpression Promotes Efficient Differentiation of Pluripotent Stem Cells to Endothelial Cells

ABSTRACT: ETV2 Overexpression Promotes Efficient Differentiation of Pluripotent Stem Cells to Endothelial Cells

PROVIDER: PRJNA1129856 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29653100_1.fastq.gz	Fastqsanger.gz
	SRR29653100_2.fastq.gz	Fastqsanger.gz
	SRR29653101_1.fastq.gz	Fastqsanger.gz
	SRR29653101_2.fastq.gz	Fastqsanger.gz
	SRR29653102_1.fastq.gz	Fastqsanger.gz

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ETV2 Overexpression Promotes Efficient Differentiation of Pluripotent Stem Cells to Endothelial Cells

Project description:Directed differentiation of endothelial cells (ECs) from human pluripotent stem cells (hPSCs) typically takes around fourteen days, requires optimization of parameters such as hPSC seeding density and medium supplement concentration or timing, and often necessitates cell sorting to achieve high purity ECs. Overexpression of cell type-specific transcription factors in hPSCs has been shown to lead to efficient differentiation of many cell types, including neurons, astrocytes and hepatocytes. ETV2 has been identified as an essential transcription factor for endothelial cell fate commitment during development. Here, we present a simple, well-characterized differentiation method to generate ECs by overexpressing ETV2 in an inducible manner (iETV2) in hPSC cell lines. The result is a two-stage differentiation strategy, in which ECs are differentiated in a basal medium during stage I and then expanded in endothelial medium during stage II. By optimizing hPSC seeding density and differentiation medium, we generated an EC population with more than 99% pure CD31+ CD144+ cells without any cell sorting in just five days. In vitro angiogenesis potential of the iETV2-ECs was confirmed in cord formation assays and iETV2-EC uptake of acetylated LDL and response to inflammatory cytokines was confirmed. We compared transcriptomics of iETV2-ECs to the ECs generated from hPSCs via directed differentiation and confirmed similarity of gene expression profiles of ECs generated by these two different approaches. Furthermore, we found that iETV2-ECs respond to previously identified Wnt signaling agonist CHIR99021 and TGFβ signaling inhibitor RepSox to acquire aspects of brain EC phenotype. These findings underscore that iETV2-ECs can serve as easily scalable endothelial source, powering a variety of research applications, potentially including in vitro blood-brain barrier modeling.

2025-03-24 | GSE271101 | GEO

Pioneer factor ETV2 safeguards endothelial cell specification

Project description:Mechanisms of cell fate specification are central to developmental biology and regenerative medicine. ETV2 is a master regulator for the endothelial cell lineage specification. Here, we study mechanisms by which ETV2 overexpression in human iPSC-derived mesodermal progenitors efficiently specifies ECs.

2025-04-01 | GSE267565 | GEO

Gene expression profiling in Vav-Etv2 KSL and Granulocyte hematopoietic cells

Project description:Etv2 transgene was expressed from ROSA26 locus by removing floxed STOP cassette by Vav Cre transgene. KSL or Mac1+/Gr1+ cells were sorted from control or Vav-Etv2 bone marrow and compared for gene expression in duplicate. This study will reveal the effect of Etv2 transgene in adult hematopoietic cells. The effect of Etv2 overexpression in relevant mouse tissue will be important to understand its effect in comparison with in ES cells. Genes aberrantly regulated by Etv2 overexpression will help to understand the caveat when using Etv2 to induce endothelial and hematopoietic cells in vitro. Sample ID #1;KSL;Control #2;KSL;Control #3;KSL;Tg #4;KSL;Tg #5;Gr;Control #6;Gr;Control #7;Gr;Tg #8;Gr;Tg

2012-05-09 | E-GEOD-36731 | biostudies-arrayexpress

Gene expression profiling in Vav-Etv2 KSL and Granulocyte hematopoietic cells

2012-05-10 | GSE36731 | GEO

cAMP/EPAC signaling enables ETV2 to induce endothelial cells with high angiogenesis potential [RNA-seq]

Project description:Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed ChIP-sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of cAMP/EPAC/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential.

2019-11-09 | GSE123907 | GEO

cAMP/EPAC signaling enables ETV2 to induce endothelial cells with high angiogenesis potential [ChIP-seq]

2019-11-09 | GSE123906 | GEO

Gene expression profiling in Tie-2-Etv2 YS hematopoietic precursors

Project description:Etv2 transgene was expressed from ROSA26 locus by removing floxed STOP cassette by Tie-2 Cre transgene.VE-Cad+/CD45+ cells were sorted from control or tie-2-Etv2 E10.5 embryosYS(yolk sac) and compared for gene expression in duplicate. This study will reveal the effect of Etv2 transgene in E10.5 mouse embryo yolk sac. The effect of Etv2 overexpression in relevant mouse tissue will be important to understand its effect in comparison with in ES cells. Genes aberrantly regulated by Etv2 overexpression will help to understand the caveat when using Etv2 to induce endothelial and hematopoietic cells in vitro. Sample ID YS- ; (VECAD+CD45+;YS;Control) YS+12; (VECAD+CD45+;YS;Tg) YS+22 ; (VECAD+CD45+;YS;Tg)

2012-05-09 | E-GEOD-36788 | biostudies-arrayexpress

Profiling gene expression of ETV2-induced vascular endothelial cells (ETVECs)

Project description:ETV2 induces expression of endothelial-specific genes in primary human adult skin fibroblasts (HAFs) Human unbillical vein endothelial cells (HUVECs) are used as a control 32 days after ETV2 induction into HAFs, cells are recognized as ETVECs. ETVECs were created from three independent skin donor. Each number of ETVEC is correspond to the number of HAF.

2013-07-19 | E-GEOD-48980 | biostudies-arrayexpress

RNA sequencing of hiPSC-derived endothelial cells via doxycycline-induced ETV2 transcription factor overexpression

Project description:RNA sequencing of hiPSC-derived endothelial cells via doxycycline-induced ETV2 transcription factor overexpression

| PRJNA793821 | ENA

Gene expression profiling in Tie-2-Etv2 YS hematopoietic precursors

2012-05-10 | GSE36788 | GEO