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Comparison of human embroynic stem cell derived vascular cells to mature human vascular and hematopoietic cells

ABSTRACT: The pathways involved in hierarchical differentiation of human embryonic stem cells (hESC) into abundant and durable endothelial cells (EC) are unknown. We employed an EC-specific VE-cadherin promoter driving GFP (hVPr-GFP) to screen for factors that augmented yields of vascular-committed ECs from hESCs. In phase 1 of our approach, inhibition of TGFb, precisely at day 7 of hESC differentiation, enhanced emergence of hVPr-GFP+ ECs by 10-fold. In the second phase, TGFb-inhibition preserved proliferation and vascular identity of purified ECs, resulting in net 36-fold expansion of homogenous EC-monolayers, and allowing transcriptional profiling that revealed a unique angiogenic signature defined by the VEGFR2highId1highVE-cadherin+EphrinB2+CD133+HoxA9- phenotype. Using an Id1-YFP hESC reporter line, we showed that TGFb-inhibition sustained Id1 expression in hESC-derived ECs, which was required for increased proliferation and preservation of EC commitment. These data provide a multiphasic method for serum-free differentiation and long-term maintenance of authentic hESC-derived ECs, establishing clinical-scale generation of transplantable human ECs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19735 | GEO | 2010/01/05

SECONDARY ACCESSION(S): PRJNA122195

REPOSITORIES: GEO

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Comparison of human embroynic stem cell derived vascular cells to mature human vascular and hematopoietic cells

Project description:The pathways involved in hierarchical differentiation of human embryonic stem cells (hESC) into abundant and durable endothelial cells (EC) are unknown. We employed an EC-specific VE-cadherin promoter driving GFP (hVPr-GFP) to screen for factors that augmented yields of vascular-committed ECs from hESCs. In phase 1 of our approach, inhibition of TGFb, precisely at day 7 of hESC differentiation, enhanced emergence of hVPr-GFP+ ECs by 10-fold. In the second phase, TGFb-inhibition preserved proliferation and vascular identity of purified ECs, resulting in net 36-fold expansion of homogenous EC-monolayers, and allowing transcriptional profiling that revealed a unique angiogenic signature defined by the VEGFR2highId1highVE-cadherin+EphrinB2+CD133+HoxA9- phenotype. Using an Id1-YFP hESC reporter line, we showed that TGFb-inhibition sustained Id1 expression in hESC-derived ECs, which was required for increased proliferation and preservation of EC commitment. These data provide a multiphasic method for serum-free differentiation and long-term maintenance of authentic hESC-derived ECs, establishing clinical-scale generation of transplantable human ECs. The experiment compared 6 sets of biological duplicates which included human embryonic stem cell derived and mature vascular cell types.

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Expression data from three endothelial cell lines derived from murine embryonic stem cells expressing VE-cadherin, N-cadherin or both

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Expression data from three endothelial cell lines derived from murine embryonic stem cells expressing VE-cadherin, N-cadherin or both

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2012-01-10 | E-GEOD-34948 | biostudies-arrayexpress

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