Author/Authors :
Ben Van Handel، نويسنده , , Amélie Montel-Hagen، نويسنده , , Rajkumar Sasidharan، نويسنده , , Haruko Nakano، نويسنده , , Roberto Ferrari، نويسنده , , Cornelis J. Boogerd، نويسنده , , Johann Schredelseker، نويسنده , , Yanling Wang، نويسنده , , Sean Hunter، نويسنده , , T?nis Org، نويسنده , , Jian Zhou، نويسنده , , Xinmin Li، نويسنده , , Matteo Pellegrini، نويسنده , , Jau-Nian Chen، نويسنده , , Stuart H. Orkin، نويسنده , , Siavash K. Kurdistani، نويسنده , , Sylvia M. Evans، نويسنده , , Atsushi Nakano، نويسنده , , Hanna K.A. Mikkola، نويسنده ,
Abstract :
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.
