Expansion and maintenance of human embryonic stem cell-derived endothelial cells by TGFΒ inhibition is Id1 dependent Academic Article uri icon


MeSH Major

  • Embryonic Stem Cells
  • Endothelial Cells
  • Inhibitor of Differentiation Protein 1
  • Signal Transduction
  • Transforming Growth Factor beta


  • Previous efforts to differentiate human embryonic stem cells (hESCs) into endothelial cells have not achieved sustained expansion and stability of vascular cells. To define vasculogenic developmental pathways and enhance differentiation, we used an endothelial cell-specific VE-cadherin promoter driving green fluorescent protein (GFP) (hVPr-GFP) to screen for factors that promote vascular commitment. In phase 1 of our method, inhibition of transforming growth factor (TGF)beta at day 7 of differentiation increases hVPr-GFP(+) cells by tenfold. In phase 2, TGFbeta inhibition maintains the proliferation and vascular identity of purified endothelial cells, resulting in a net 36-fold expansion of endothelial cells in homogenous monolayers, which exhibited a transcriptional profile of Id1(high)VEGFR2(high)VE-cadherin(+) ephrinB2(+). Using an Id1-YFP hESC reporter line, we showed that TGFbeta inhibition sustains Id1 expression in hESC-derived endothelial cells and that Id1 is required for increased proliferation and preservation of endothelial cell commitment. Our approach provides a serum-free method for differentiation and long-term maintenance of hESC-derived endothelial cells at a scale relevant to clinical application.

publication date

  • February 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2931334

Digital Object Identifier (DOI)

  • 10.1038/nbt.1605

PubMed ID

  • 20081865

Additional Document Info

start page

  • 161

end page

  • 6


  • 28


  • 2