BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway

Hao Bai, Yongxing Gao, Melanie Arzigian, Don M. Wojchowski, Wen Shu Wu, Zack Z. Wang

Research output: Contribution to journalArticlepeer-review

Abstract

The signals that direct pluripotent stem cell differentiation into lineage-specific cells remain largely unknown. Here, we investigated the roles of BMP on vascular progenitor development from human embryonic stem cells (hESCs). In a serum-free condition, hESCs sequentially differentiated into CD34+CD31-, CD34+CD31+, and then CD34-CD31+ cells during vascular cell development. CD34+CD31+ cells contained vascular progenitor population that gives rise to endothelial cells and smooth muscle cells. BMP4 promoted hESC differentiation into CD34+CD31+ cells at an early stage. In contrast, TGFβ suppressed BMP4-induced CD34+CD31+ cell development, and promoted CD34+CD31- cells that failed to give rise to either endothelial or smooth muscle cells. The BMP-Smad inhibitor, dorsomorphin, inhibited phosphorylation of Smad1/5/8, and blocked hESC differentiation to CD34+CD31+ progenitor cells, suggesting that BMP Smad-dependent signaling is critical for CD34+CD31+ vascular progenitor development. Our findings provide new insight into how pluripotent hESCs differentiate into vascular cells.

Original languageEnglish (US)
Pages (from-to)363-374
Number of pages12
JournalJournal of cellular biochemistry
Volume109
Issue number2
DOIs
StatePublished - Feb 1 2010

Keywords

  • BMP4
  • Endothelial cells
  • Human embryonic stem cells
  • Smooth muscle cells
  • TGFβ

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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