title: Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells.
abstract: Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity. The developmental sources of these cells and molecular mechanisms controlling their progenitors in the heart are only partially understood. Here we show that endocardial endothelial cells are progenitors of pericytes and vascular smooth muscle cells in the murine embryonic heart. Endocardial cells undergo endothelial-mesenchymal transition and convert into primitive mesenchymal progenitors expressing the platelet-derived growth factor receptors, PDGFRα and PDGFRβ. These progenitors migrate into the myocardium, differentiate and assemble the wall of coronary vessels, which requires canonical Wnt signalling involving Frizzled4, β-catenin and endothelial cell-derived Wnt ligands. Our findings identify a novel and unexpected population of progenitors for coronary mural cells with potential relevance for heart function and disease conditions.
authors: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors: Qi
authors: 0000-0001-8485-6540
authors: Q
authors: Chen
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Hui
authors: H
authors: Zhang
authors: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors: Yang
authors: Y
authors: Liu
authors: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors: Susanne
authors: S
authors: Adams
authors: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors: Hanna
authors: H
authors: Eilken
authors: Electron Microscopy and Flow Cytometry Units, Max Planck Institute for Molecular Biomedicine, D-48149 Münster, Germany.
authors: Martin
authors: M
authors: Stehling
authors: IFOM Fondazione, FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
authors: Monica
authors: M
authors: Corada
authors: IFOM Fondazione, FIRC Institute of Molecular Oncology, 20139 Milan, Italy.|Department of Biosciences, University of Milan, 20133 Milan, Italy.
authors: Elisabetta
authors: E
authors: Dejana
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Bin
authors: B
authors: Zhou
authors: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors: Ralf H
authors: 0000-0003-3031-7677
authors: RH
authors: Adams
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004699:Endocardium / Q000166:cytology / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006321:Heart / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D020286:Pericytes / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta