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

Qi Chen,Martin Stehling,Yang Liu,Elisabetta Dejana,Hui Zhang,Ralf H Adams,Susanne Adams,Hanna Eilken,Bin Zhou,Monica Corada

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.

Highlights

Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity
platelet-derived growth factor receptor b (PDGFRb) þ cells and their progeny were stably labelled with Pdgfrb(BAC)-CreERT2 transgenic mice, which were recently generated by our group
These mouse lines (Supplementary Table 1) in combination with immunostaining showed that the majority of mural cells associated with coronary capillaries were positive for platelet-derived growth factor receptor b (PDGFRb) and the proteoglycan NG2 but lacked PDGFRa expression (Supplementary Fig. 1a–e)

Summary

Introduction

Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity. Mural cells stabilize vessels through physical and molecular interactions with adjacent ECs, and absence of mural cells leads to vascular leakage and haemorrhaging[3,4,7] Pericytes and their progenitors have high clinical relevance and, several studies have explored the potential of these cells for cardiac regeneration and heart tissue engineering[10,11,12,13,14,15]. Inactivation of the Pdgfrb gene (encoding PDGFRb) in epicardial cells did not eliminate all cardiac mural cells[21] arguing for additional, so far unknown developmental sources of pericytes and vSMCs in the heart. We have identified endocardial ECs as novel progenitors for mural cells in the heart with the help of genetic lineage tracing and gene inactivation experiments. Mural and endothelial cells develop from a common progenitor population during early stages of heart development

Methods

Results

Conclusion