title: Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium.
abstract: 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.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Handel
authors.forename: Amélie
authors.initials: A
authors.lastname: Montel-Hagen
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Sasidharan
authors.forename: Haruko
authors.initials: H
authors.lastname: Nakano
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Boogerd
authors.forename: Johann
authors.initials: J
authors.lastname: Schredelseker
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.forename: Sean
authors.initials: S
authors.lastname: Hunter
authors.forename: Tõnis
authors.initials: T
authors.lastname: Org
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Jau-Nian
authors.initials: JN
authors.lastname: Chen
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.forename: Siavash K
authors.initials: SK
authors.lastname: Kurdistani
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Hanna K A
authors.initials: HK
authors.lastname: Mikkola
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D004730:Endothelium, Vascular / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D055018:Hemangioblasts; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology; D010920:Placenta / Q000098:blood supply; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000378:metabolism; D015017:Yolk Sac / Q000098:blood supply
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D050676:Core Binding Factor Alpha 2 Subunit; D060850:LIM-Homeodomain Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C493726:Runx1 protein, mouse; C489366:Tal1 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1