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Adaptable durable human endothelial cells for organogenesis and tumorigenesis

ABSTRACT: ETV2 resets endothelial cells' fate, confering them with vascular mallebility, which results in long-term stable vessel formation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147746 | GEO | 2020/03/31

REPOSITORIES: GEO

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Adaptable durable human endothelial cells for organogenesis and tumorigenesis

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Efficient direct reprogramming of c-Kit− mature amniotic cells into endothelial cells by ETS factors and TGFβ suppression

Project description:ETS transcription factors ETV2, FLI1 and ERG1 specify pluripotent stem cells into endothelial cells (PSC-ECs). However, these PSC-ECs are unstable and often drift towards non-vascular cell fates. We show that human mid-gestation c-Kit- lineage-committed amniotic cells (ACs) can be reprogrammed into induced vascular endothelial cells (rAC-VECs). Transient ETV2 expression in ACs generated immature iVECs, while co-expression with FLI1/ERG1 endowed rAC-VECs with a vascular repertoire and morphology matching mature ECs. Brief TGFb-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and non-vascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Thus, short-term ETV2 expression and TGFb-inhibition along with constitutive ERG1/FLI1 co-expression reprogram mature ACs into generic rAC-VECs with clinical-scale expansion potential. Public banking of HLA-typed rAC-VECs would establish a vascular inventory for treatment of genetically diverse disorders. Transcriptome sequencing of clonal and non-clonal rAC-VECs, HUVECs, LSECs, CD34+/Lin-, BMS

2012-10-30 | E-GEOD-40291 | biostudies-arrayexpress

Efficient direct reprogramming of c-Kit− mature amniotic cells into endothelial cells by ETS factors and TGFβ suppression

2012-10-30 | GSE40291 | GEO

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

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