Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart

We identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium, an epithelial sheet overlying the heart

Bin Zhou; Qing Ma; Satish Rajagopal; Sean M. Wu; Ibrahim Domian; José Rivera-Feliciano; Dawei Jiang; Alexander von Gise; Sadakatsu Ikeda; Kenneth R. Chien; William T. Pu


Scholarcy highlights

  • Epicardial cells migrate from the proepicardium, an outgrowth of the septum transversum, and spread over the surface of the heart
  • Consistent with prior reports showing that epicardially-derived mesenchyme predominately differentiates into smooth muscle cells in mammals, most Wt1-derived cells adopted a SMC fate, and a minority differentiated into endothelial cells
  • We obtained additional independent evidence that epicardial cells differentiate into cardiomyocytes by selective dye labeling of epicardium in E11.5 explanted hearts
  • To further investigate the relationship of Nkx and Wt1 expression, we studied the expression of Wt1 in Nkx2-5+ cells during embryoid body differentiation of embryonic stem cells
  • Consistent with the capacity of Wt1-expressing cells to differentiate into CMs, Wt1+ PE/ epicardial cells are derived from progenitors that express Nkx and Isl, suggesting that they share a common developmental origin with previously described multipotent cardiogenic progenitors 1,2
  • Immunohistochemistry was performed according to standard methods, using primary and secondary antibodies listed in Supplementary Table 1

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