title: The heart endocardium is derived from vascular endothelial progenitors.
abstract: The embryonic heart is composed of two cell layers: the myocardium, which contributes to cardiac muscle tissue, and the endocardium, which covers the inner lumen of the heart. Whereas significant progress has been made toward elucidating the embryonic origins of the myocardium, the origins of the endocardium remain unclear. Here, we have identified an endocardium-forming field medial to the cardiac crescent, in a continuum with the endothelial plexus. In vivo live imaging of quail embryos revealed that endothelial progenitors, like second/anterior heart field progenitors, migrate to, and enter, the heart from the arterial pole. Furthermore, embryonic endothelial cells implanted into the cardiac crescent contribute to the endocardium, but not to the myocardium. In mouse, lineage analysis focusing on endocardial cells revealed an unexpected heterogeneity in the origins of the endocardium. To gain deeper insight into this heterogeneity, we conditionally ablated Flk1 in distinct cardiovascular progenitor populations; FLK1 is required in vivo for formation of the endocardium in the Mesp1 and Tie2 lineages, but not in the Isl1 lineage. Ablation of Flk1 coupled with lineage analysis in the Isl1 lineage revealed that endothelium-derived Isl1(-) endocardial cells were significantly increased, whereas Isl1(+) endocardial cells were reduced, suggesting that the endocardium is capable of undergoing regulative compensatory growth. Collectively, our findings demonstrate that the second heart field contains distinct myocardial and endocardial progenitor populations. We suggest that the endocardium derives, at least in part, from vascular endothelial cells.
authors: Department of Biological Regulation, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors: Michal
authors: M
authors: Milgrom-Hoffman
authors: Zachary
authors: Z
authors: Harrelson
authors: Napoleone
authors: N
authors: Ferrara
authors: Elazar
authors: E
authors: Zelzer
authors: Sylvia M
authors: SM
authors: Evans
authors: Eldad
authors: E
authors: Tzahor
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology; D002642:Chick Embryo; D002678:Chimera; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D004699:Endocardium / Q000166:cytology / Q000196:embryology*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006321:Heart / Q000033:anatomy & histology* / Q000196:embryology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000166:cytology; D011784:Quail; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D060850:LIM-Homeodomain Proteins; D042787:Receptor, TIE-2; D014157:Transcription Factors; D040301:Vascular Endothelial Growth Factor Receptor-2; C101538:Mesp1 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1