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ER71/ETV2-mediated direct reprogramming of human dermal fibroblasts (HDFs) into endothelial-like cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE50801 | GEO | 2013/09/12

SECONDARY ACCESSION(S): PRJNA219041

REPOSITORIES: GEO

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ER71/ETV2-mediated direct reprogramming of human dermal fibroblasts (HDFs) into endothelial-like cells

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

Genome-wide analysis of ETS factor ER71/ETV2 chromatin occupancy

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

Genome-wide analysis of ETS factor ER71/ETV2 chromatin occupancy

2015-03-30 | GSE59402 | GEO

Homo sapiens

Project description:ER71/ETV2-mediated direct reprogramming of human dermal fibroblasts (HDFs) into endothelial-like cells

| PRJNA219041 | ENA

Gene expression analysis of inducible ES cells overexpressing Etv2 (induced for 12 hours at day 3 of differentiation)

Project description:During embryogenesis, the endothelial and the hematopoietic lineages first appear during gastrulation in the blood island of the yolk sac. We have previously reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic and endothelial lineages, however, the precise roles of Etv2 in yolk sac development remains unclear. We carried out a transcriptome analysis using an ES cell line that can inducibly express Etv2. Cells were induced for 12 hours at day 3 of differentiation. An ES cell line (dervied from mouse of background strain 129P2/Ola) with a doxycycline inducible expression casette of Etv2 (ER71 A2Lox.cre) was differentiated in hanging drops. At 3 days of differentiation, cells were treated with doxycycline for 12 hours, and subsequently Flk1(+) cells were sorted. Experiment was done in triplicate and untreated cells were used for control.

2012-07-03 | E-GEOD-37658 | biostudies-arrayexpress

Hemangioblast skewing from embryonic stem(ES) cells by defined factors

Project description:Successful derivation of a specific cell lineage from pluripotent stem cells will tremendously facilitate the clinical usage of pluripotent stem derived somatic cells. Herein, we demonstrate that ER71/Etv2, GATA2 and Scl form a core network in hemangioblast development and that transient co-expression of these three factors robustly induced hemangioblasts from ES cells. Such induced hemangioblasts potently generated hematopoietic and endothelial cells in culture as well as in vivo, warranting the evaluation of these cells in the future for repairing and/or regenerating hematopoietic and/or angiogenic defects. We have established a doxycycline inducible ES cell, iEGS, in which ER71/Etv2, GATA2 three transcription factors can be transiently co-expressed by doxycycline induction. We further analyzed the downstream target genes and signaling pathways at 6, 12 and 24hrs after ER71/Etv2, GATA2 induction. These data were obtained from three independent experiments.

2014-02-03 | E-GEOD-45147 | biostudies-arrayexpress

Gene expression analysis of inducible ES cells overexpressing Etv2 (induced for 12 hours at day 3 of differentiation)

2012-07-04 | GSE37658 | GEO

Transcriptional profile of ER71 EYFP positive/negative cells in ER71 WT and MT embryos

Project description:ER71 mutant embryos are nonviable and lack hematopoietic and endothelial lineages. To further define the functional role for ER71 in cell lineage decisions, we generated genetically modified mouse models. We engineered an ER71-EYFP transgenic mouse model by fusing the 3.9 kb ER71 promoter to the EYFP reporter gene. Using FACS and transcriptional profiling, we examined the EYFP+ populations of cells in ER71 mutant and wildtype littermates. In the absence of ER71, we observed an increase in the number of EYFP expressing cells, increased expression of the cardiac molecular program and decreased expression of the hemato-endothelial program compared to the wildtype littermate controls. We have also generated a novel ER71-Cre transgenic mouse model using the same 3.9 kb ER71 promoter. Genetic fate mapping studies revealed that the ER71 expressing cells daughter hematopoietic and endothelial lineages in the wildtype background. In the absence of ER71, these cell populations contributed to alternative mesodermal lineages including the cardiac lineage. To extend these analyses, we used an inducible ES/EB system and observed that ER71 overexpression repressed cardiogenesis. Together, these studies identify ER71 as a critical regulator of mesodermal fate decisions, acting to specify the hematopoietic and endothelial lineages at the expense of cardiac lineages. This enhances our understanding of the mechanisms that govern mesodermal fate decisions early during embryogenesis.

2011-11-02 | GSE32223 | GEO

Hemangioblast skewing from embryonic stem(ES) cells by defined factors

2014-02-03 | GSE45147 | GEO

Transcriptional profile of ER71 EYFP positive/negative cells in ER71 WT and MT embryos

2011-11-02 | E-GEOD-32223 | biostudies-arrayexpress