Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells

Nat Commun. 2016 Aug 12:7:12422. doi: 10.1038/ncomms12422.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Endocardium / cytology
  • Endocardium / physiology
  • Endothelial Cells / physiology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Heart / physiology
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Animal
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology
  • Myocardium / cytology
  • Myocytes, Smooth Muscle / physiology*
  • Pericytes / physiology*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism

Substances

  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta