| First Author | Van Handel B | Year | 2012 |
| Journal | Cell | Volume | 150 |
| Issue | 3 | Pages | 590-605 |
| PubMed ID | 22863011 | Mgi Jnum | J:187883 |
| Mgi Id | MGI:5438687 | Doi | 10.1016/j.cell.2012.06.026 |
| Citation | Van Handel B, et al. (2012) Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium. Cell 150(3):590-605 |
| abstractText | 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+Pdgfralpha+ 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 Scl(fl/fl)Rosa26Cre-ER(T2) 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. |
