ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment
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ABSTRACT:
PROVIDER: PRJNA563075 | ENA |
REPOSITORIES: ENA
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Project description:The lineage-determining transcription factor ETV2 is necessary and sufficient for hematoendothelial fate commitment. We investigated how ETV2-driven gene regulatory networks promote hematoendothelial fate commitment. We resolved the sequential determination steps of hematoendothelial versus cardiac differentiation from mouse embryonic stem cells. Etv2 was strongly induced and bound to the enhancers of hematoendothelial genes in a common cardiomyocyte-hematoendothelial mesoderm progenitor. However, only Etv2 itself and Tal1, not other ETV2-bound genes, were induced. Despite ETV2 genomic binding and Etv2 and Tal1 expression, cardiomyogenic fate potential was maintained. A second wave of ETV2-bound target genes was up-regulated during the transition from the common cardiomyocyte-hematoendothelial progenitor to the committed hematoendothelial population. A third wave of ETV-bound genes were subsequently expressed in the committed hematoendothelial population for sub-lineage differentiation. The shift from ETV2 binding to productive transcription, not ETV2 binding to target gene enhancers, drove hematoendothelial fate commitment. This work identifies mechanistic phases of ETV2-dependent gene expression that distinguish hematoendothelial specification, commitment, and differentiation.
2023-06-16 | GSE136692 | GEO
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: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.
2011-08-31 | GSE31743 | GEO
Project description:A comprehensive understanding of a lineage map and molecular mechanisms underlying lineage specification is fundamental to development. To this end, ETS transcription factor Etv2 functions as the master regulator of hematopoietic and endothelial cell formation. As such, Etv2 regulated hemangiogenesis provides an excellent model for assessing cell lineage specification. Herein, we generated several reporter embryonic stem (ES) cell lines to map developmental route pertaining to hemangiogenesis. We performed transcriptome analysis and high throughput CRISPR screening to further delineate molecular mechanisms regulating hemangiogenic lineage specification. We show a distinct lineage map of hemangiogenesis, in which hemangiogenic fate is specified not simply by the onset of Etv2 expression, but in a threshold-dependent manner. Importantly, VEGF-FLK1 signaling is necessary for efficiently achieving ETV2-threshold. Moreover, we find forkhead transcription factor Foxh1 to be required for FLK1 mesoderm formation. These studies provide a roadmap in hematopoietic and vascular cell generation and applications in regenerative medicine.
2017-08-01 | GSE85641 | GEO
Project description:Enhancers orchestrate gene expression programs that drive multicellular development and lineage commitment. Thus, genetic variants at enhancers are thought to contribute to developmental diseases by altering cell fate commitment. However, while many variant-containing enhancers have been identified, systematic studies to endogenously test the impact of these enhancers on lineage commitment have been lacking. We performed a single-cell CRISPRi screen to directly assess the roles of 25 enhancers and putative cardiac target genes implicated in genetic studies of congenital heart defects (CHD). We identified 16 enhancers whose repression leads to delayed differentiation of human cardiomyocytes. A focused analysis on 6 TBX5 enhancers showed that TBX5 enhancer perturbation delays the transcriptional switch from mid-CM to late-CM states. Knockout of two TBX5 enhancers resulted in X and Y, which phenocopy expected CHD phenotypes. Together, these results identify critical enhancers of cardiac development and suggest that misregulation of these enhancers could contribute to cardiac defects in human patients.
2022-05-15 | GSE190475 | GEO
Project description:CHD-associated enhancers direct human cardiomyocyte lineage commitment.
| PRJNA787259 | ENA
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
Project description:ILC2 development requires GATA3-related super-enhancers after lineage commitment
| PRJNA902420 | ENA
Project description:We discover that ER71/ETV2 initiates hemangiogenic program by activating blood and endothelial cell lineage specifying genes while enhancing FLK1 expression and expanding hemangioblast population. Furthermore, ER71/ETV2 establishes an ETS hierarchy by directly activating Ets genes in hematopoietic and endothelial cell lineage development. As such, ER71/ETV2-initiated blood and endothelial cell program is maintained by ER71/ETV2 downstream ETS factors through an ETS switching mechanism. ChIP-seq analysis of ER71 in differentiated embryonic stem cells
2015-03-30 | E-GEOD-59402 | biostudies-arrayexpress
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