2008 July 3 | Bin Zhou, Qing Ma, Satish Rajagopal, Sean M. Wu, Ibrahim Domian, José Rivera-Feliciano, Dawei Jiang, Alexander von Gise, Sadakatsu Ikeda, Kenneth R. Chien, and William T. Pu
A subset of Wt1-expressing cells in the epicardium contribute to the cardiomyocyte lineage during heart development. These cells, previously unrecognized as cardiomyocyte progenitors, arise from multipotent Nkx2-5 and Isl1-expressing progenitors. Wt1-expressing epicardial cells migrate to the myocardium and differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells. In vivo and in vitro studies show that Wt1-expressing cells can generate functional cardiomyocytes, as evidenced by co-expression of lineage tracers and cardiomyocyte markers such as cardiac troponin T (Tnnt2) and sarcomeric actinin (Actn1). These cells also exhibit functional properties of cardiomyocytes, including spontaneous contractile activity and calcium oscillations. Furthermore, they are electrically coupled to neighboring cardiomyocytes through gap junction proteins like connexin 43 (Cx43). These findings suggest that Wt1-expressing cells in the epicardium are a previously unrecognized source of cardiomyocyte progenitors. The study also shows that these cells share a developmental origin with multipotent cardiogenic progenitors, indicating a common lineage. This discovery provides a foundation for future research on using these progenitors for cardiac regeneration and repair.A subset of Wt1-expressing cells in the epicardium contribute to the cardiomyocyte lineage during heart development. These cells, previously unrecognized as cardiomyocyte progenitors, arise from multipotent Nkx2-5 and Isl1-expressing progenitors. Wt1-expressing epicardial cells migrate to the myocardium and differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells. In vivo and in vitro studies show that Wt1-expressing cells can generate functional cardiomyocytes, as evidenced by co-expression of lineage tracers and cardiomyocyte markers such as cardiac troponin T (Tnnt2) and sarcomeric actinin (Actn1). These cells also exhibit functional properties of cardiomyocytes, including spontaneous contractile activity and calcium oscillations. Furthermore, they are electrically coupled to neighboring cardiomyocytes through gap junction proteins like connexin 43 (Cx43). These findings suggest that Wt1-expressing cells in the epicardium are a previously unrecognized source of cardiomyocyte progenitors. The study also shows that these cells share a developmental origin with multipotent cardiogenic progenitors, indicating a common lineage. This discovery provides a foundation for future research on using these progenitors for cardiac regeneration and repair.