Endothelial cells regulate cardiomyocyte development from embryonic stem cells

Kang Chen, Hao Bai, Melanie Arzigian, Yong Xing Gao, Jing Bao, Wen Shu Wu, Wei Feng Shen, Liqun Wu, Zack Z. Wang

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The molecules and environment that direct pluripotent stem cell differentiation into cardiomyocytes are largely unknown. Here, we determined a critical role of receptor tyrosine kinase, EphB4, in regulating cardiomyocyte generation from embryonic stem (ES) cells through endothelial cells. The number of spontaneous contracting cardiomyocytes, and the expression of cardiac-specific genes, including α-MHC and MLC-2V, was significantly decreased in EphB4-null ES cells. EphB4 was expressed in endothelial cells underneath contracting cardiomyocytes, but not in cardiomyocytes. Angiogenic inhibitors, including endostatin and angiostatin, inhibited endothelial cell differentiation and diminished cardiomyogenesis in ES cells. Generation of functional cardiomyocytes and the expression of cardiac-specific genes were significantly enhanced by co-culture of ES cells with human endothelial cells. Furthermore, the defects of cardiomyocyte differentiation in EphB4-deficient ES cells were rescued by human endothelial cells. For the first time, our study demonstrated that endothelial cells play an essential role in facilitating cardiomyocyte differentiation from pluripotent stem cells. EphB4 signaling is a critical component of the endothelial niche to regulate regeneration of cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalJournal of cellular biochemistry
Issue number1
StatePublished - Sep 1 2010
Externally publishedYes


  • Cardiomyocytes
  • Embryonic Stem (ES) cells
  • Endothelial cells
  • EphB4
  • Ephrin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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