Pioneer factor ETV2 safeguards endothelial cell specification
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1111882 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29044405_1.fastq.gz | Fastqsanger.gz | |||
| SRR29044405_2.fastq.gz | Fastqsanger.gz | |||
| SRR29044406_1.fastq.gz | Fastqsanger.gz | |||
| SRR29044406_2.fastq.gz | Fastqsanger.gz | |||
| SRR29044407_1.fastq.gz | Fastqsanger.gz |
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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
Project description:The ability to differentiate human induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseases in vitro. The mechanisms underlying the specification of these cell types during human development are not well-understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA sequencing data revealed differential ETV2 dynamics in the two lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on the in vitro differentiation dynamics of two important cardiac lineages.
2023-01-20 | GSE157954 | GEO
Project description:The ability to differentiate human induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseases in vitro. The mechanisms underlying the specification of these cell types during human development are not well-understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA sequencing data revealed differential ETV2 dynamics in the two lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on the in vitro differentiation dynamics of two important cardiac lineages.
2023-01-20 | GSE202901 | GEO
Project description:The vasculature is an essential organ for the delivery of blood and oxygen to all tissues of the body and thus relevant to the treatment of ischemic diseases, injury-induced regeneration, and solid tumor growth. Therefore, the definition of pioneer factors and regulatory pathways that govern the specification and differentiation of endothelial progenitors will serve as a platform for targeted therapies to promote cardiovascular regeneration and treatment of solid organ tumors. Previously, we demonstrated that ETV2 was an essential transcription factor for the development of cardiac, endothelial and hematopoietic lineages. Here, we report that ETV2 functions as a novel pioneer factor that relaxes closed chromatin and regulates endothelial development. By comparing engineered embryonic stem cell differentiation and reprogramming models with single cell RNA-seq, ATAC-seq and ChIP-seq techniques, we demonstrated that ETV2 was able to bind nucleosomal DNA and function as a pioneer factor independent of the cellular context. We determined that ETV2 executes a pioneering role by recruiting BRG1 to remodel chromatin around endothelial genes and help maintain an open configuration. ETV2 chromatin binding also resulted in increased H3K27ac deposition. Collectively, these results will serve as a platform for the development of therapeutic initiatives directed towards cardiovascular and oncological diseases.
2022-10-04 | GSE185681 | GEO
Project description:The vasculature is an essential organ for the delivery of blood and oxygen to all tissues of the body and thus relevant to the treatment of ischemic diseases, injury-induced regeneration, and solid tumor growth. Therefore, the definition of pioneer factors and regulatory pathways that govern the specification and differentiation of endothelial progenitors will serve as a platform for targeted therapies to promote cardiovascular regeneration and treatment of solid organ tumors. Previously, we demonstrated that ETV2 was an essential transcription factor for the development of cardiac, endothelial and hematopoietic lineages. Here, we report that ETV2 functions as a novel pioneer factor that relaxes closed chromatin and regulates endothelial development. By comparing engineered embryonic stem cell differentiation and reprogramming models with single cell RNA-seq, ATAC-seq and ChIP-seq techniques, we demonstrated that ETV2 was able to bind nucleosomal DNA and function as a pioneer factor independent of the cellular context. We determined that ETV2 executes a pioneering role by recruiting BRG1 to remodel chromatin around endothelial genes and help maintain an open configuration. ETV2 chromatin binding also resulted in increased H3K27ac deposition. Collectively, these results will serve as a platform for the development of therapeutic initiatives directed towards cardiovascular and oncological diseases.
2022-01-12 | GSE185682 | GEO
Project description:The vasculature is an essential organ for the delivery of blood and oxygen to all tissues of the body and thus relevant to the treatment of ischemic diseases, injury-induced regeneration, and solid tumor growth. Therefore, the definition of pioneer factors and regulatory pathways that govern the specification and differentiation of endothelial progenitors will serve as a platform for targeted therapies to promote cardiovascular regeneration and treatment of solid organ tumors. Previously, we demonstrated that ETV2 was an essential transcription factor for the development of cardiac, endothelial and hematopoietic lineages. Here, we report that ETV2 functions as a novel pioneer factor that relaxes closed chromatin and regulates endothelial development. By comparing engineered embryonic stem cell differentiation and reprogramming models with single cell RNA-seq, ATAC-seq and ChIP-seq techniques, we demonstrated that ETV2 was able to bind nucleosomal DNA and function as a pioneer factor independent of the cellular context. We determined that ETV2 executes a pioneering role by recruiting BRG1 to remodel chromatin around endothelial genes and help maintain an open configuration. ETV2 chromatin binding also resulted in increased H3K27ac deposition. Collectively, these results will serve as a platform for the development of therapeutic initiatives directed towards cardiovascular and oncological diseases.
2022-01-12 | GSE185683 | GEO
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
Project description:Screening for genes up in Etv2+ cells within Flk-1+ ES derived mesoderm Microarray analysis performed to screen for the candidate genes regulated by Etv2. Differentiated Flk-1+ mesoderm can be devided into Etv2+ or-. Etv2+ cells are assumed to be committed to hemato/endothelial cells. Comparison of two populations can reveal genes relevant in this commitment. Extract RNA from sorted Flk-1+/Etv2- vs Flk-1+/Etv2+ populations.Etv2-Venus KI ES cells were differentiated on OP9 for 4-5 days and Flk-1+ population was separated into Etv2-Venus+ or- cells. Total RNA was purified from each population for analysis.
2011-08-30 | E-GEOD-31743 | biostudies-arrayexpress
Project description:Samples 1-6: HDFs transduced with ER71/ETV2 were sorted on KDR expression at day 7. The isolated KDR+ cells together with human umbilical venous endothelial cells (HUVECs) and untransduced HDFs were subjected to genomic gene expression profiling. A significant number of genes related with vessel development and angiogenesis was significantly upregulated in KDR+ cells, compared to control HDFs. These findings strongly argue that ER71/ETV2 directly reprograms human fibroblasts to functional endothelial-like cells, which could be useful for disease investigation as well as autologous cell therapy. Samples 7-12: HDFs transduced with ER71/ETV2 were sorted on KDR expression at day 7. The isolated KDR+ cells were further cultured up to day 93. The further cultured cells together with human umbilical venous endothelial cells (HUVECs) and untransduced HDFs were subjected to genomic gene expression profiling. A significant number of genes related with vessel development and angiogenesis was significantly upregulated in the further cultured cells, compared to control HDFs. These findings strongly argue that ER71/ETV2 directly reprograms human fibroblasts to functional endothelial-like cells, which could be useful for disease investigation as well as autologous cell therapy. Samples 1-6: HDFs transduced with ER71/ETV2 were sorted on KDR expression at day 7. The isolated KDR+ cells together with human umbilical venous endothelial cells (HUVECs) and untransduced HDFs were subjected to genomic gene expression profiling. Samples 7-12: HDFs transduced with ER71/ETV2 were sorted on KDR expression at day 7. The isolated KDR+ cells were further cultured up to day 93. The further cultured cells together with human umbilical venous endothelial cells (HUVECs) and untransduced HDFs were subjected to genomic gene expression profiling.
2013-09-12 | E-GEOD-50801 | biostudies-arrayexpress
Project description:ETV2 upregulation marks the specification of early cardiomyocytes and endothelial cells during co-differentiation
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