| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2035702 | Cell | 2012 | 16 Pages |
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 full-size imageDownload 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
