Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium

SummaryEndothelium 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.

Graphical AbstractFigure optionsDownload high-quality image (257 K)Download as PowerPoint slideHighlights
► Scl establishes hemogenic endothelium and prevents its conversion to cardiac fate
► Scl inhibits precocious cardiomyocyte differentiation of endocardium in the heart
► Scl repression of cardiomyogenesis is cell intrinsic and temporally defined
► Ectopic cardiomyogenesis in Scl-deficient tissues is promoted by Wnt antagonism