Efficient differentiation of human pluripotent stem cells to endothelial progenitors via small-molecule activation of WNT signaling

Xiaojun Lian, Xiaoping Bao, Abraham Al-Ahmad, Jialu Liu, Yue Wu, Wentao Dong, Kaitlin K. Dunn, Eric V. Shusta, Sean P. Palecek

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs via GSK3 inhibition and culture in defined media to direct hPSC differentiation to CD34+CD31+ endothelial progenitors. Exogenous vascular endothelial growth factor (VEGF) treatment was dispensable, and endothelial progenitor differentiation was b-catenin dependent. Furthermore, by clonal analysis, we showed that CD34+CD31+CD117+TIE-2+ endothelial progenitors were multipotent, capable of differentiating into calponin-expressing smooth muscle cells and CD31+CD144+vWF+I-CAM1+ endothelial cells. These endothelial cells were capable of 20 population doublings, formed tube-like structures, imported acetylated low-density lipoprotein, and maintained a dynamic barrier function. This study provides a rapid and efficient method for production of hPSC-derived endothelial progenitors and endothelial cells and identifies WNT/b-catenin signaling as a primary regulator for generating vascular cells from hPSCs.

Original languageEnglish (US)
Pages (from-to)804-816
Number of pages13
JournalStem Cell Reports
Volume3
Issue number5
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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