Journal
CELL
Volume 150, Issue 3, Pages 590-605Publisher
CELL PRESS
DOI: 10.1016/j.cell.2012.06.026
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Funding
- California Institute for Regenerative Medicine (CIRM) New Faculty Award
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Innovation Award
- NIH [HL097766-01]
- Ruth L. Kirschstein National Research Service Award [GM07185]
- NIH/National Heart, Lung, and Blood Institute [T32 HL69766]
- European Molecular Biology Organisation
- Human Frontier Science Program
- CIRM
- Netherlands Organization for Scientific Research [825.10.016]
- European Union [MJD284]
- Center of Excellence in Molecular Hematology award from the National Institute of Diabetes and Digestive and Kidney Diseases
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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(+)Pdgfr alpha(+) 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-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.
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