Authors:
Ben Van Handel, Amélie Montel-Hagen, Rajkumar Sasidharan, Haruko Nakano, Roberto Ferrari, Cornelis J. Boogerd, Johann Schredelseker, Yanling Wang, Sean Hunter, Tõnis Org, Jian Zhou, Xinmin Li, Matteo Pellegrini, Jau-Nian Chen, Stuart H. Orkin, Siavash K. Kurdistani, Sylvia M. Evans, Atsushi Nakano, & Hanna K.A. Mikkola
Summary:
Endothelium in embryonic hematopoietic tissues generates hematopoietic stem/progenitor cells; however, it is unknown how its unique potential is specified. We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoietic transcriptional program in hemogenic endothelium and preventing its misspecification to a cardiomyogenic fate. Scl/ embryos activated a cardiac transcriptional program in yolk sac endothelium, leading to the emergence of CD31+Pdgfrα+ cardiogenic precursors that generated spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in Scl/ hearts, where the disorganized endocardium precociously differentiated into cardiomyocytes. Induction of mosaic deletion of Scl in Sclfl/flRosa26Cre-ERT2 embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent cardiomyogenesis from endothelium. Scl/ endothelium also upregulated the expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation of ectopic cardiogenic cells. These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells.
Source:
Cell; Vol. 150, Issue 3, 590-605 (08/03/12)