Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium
Copyright policy )Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium
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 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.
- Howard Hughes Medical Institute United States
- Harvard University United States
- Harvard Medical School United States
- Department of Microbiology United States
- University of California Los Angeles
Receptor, Platelet-Derived Growth Factor alpha, Biochemistry, Genetics and Molecular Biology(all), Hemangioblasts, Placenta, LIM-Homeodomain Proteins, Gene Expression Regulation, Developmental, Heart, Cadherins, Hematopoietic Stem Cells, Mesoderm, Platelet Endothelial Cell Adhesion Molecule-1, Mice, Pregnancy, Proto-Oncogene Proteins, 616, Core Binding Factor Alpha 2 Subunit, Basic Helix-Loop-Helix Transcription Factors, Animals, Female, Myocytes, Cardiac, Endothelium, Vascular, T-Cell Acute Lymphocytic Leukemia Protein 1
Receptor, Platelet-Derived Growth Factor alpha, Biochemistry, Genetics and Molecular Biology(all), Hemangioblasts, Placenta, LIM-Homeodomain Proteins, Gene Expression Regulation, Developmental, Heart, Cadherins, Hematopoietic Stem Cells, Mesoderm, Platelet Endothelial Cell Adhesion Molecule-1, Mice, Pregnancy, Proto-Oncogene Proteins, 616, Core Binding Factor Alpha 2 Subunit, Basic Helix-Loop-Helix Transcription Factors, Animals, Female, Myocytes, Cardiac, Endothelium, Vascular, T-Cell Acute Lymphocytic Leukemia Protein 1
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