PDGFRA is essential for the development of a novel cardiac cell type with stem-like properties

Abstract

Background We recently described a novel adult stem-like cell. Cardiac mesenchymal stromal cells (cMSCs) are phenotypically similar to MSCs from other organs, showing long-term growth and broad differentiation potential in vitro. In vivo transplantation assays demonstrate cardiomyocyte, endothelial and smooth muscle differentiation. Platelet-derived growth factor receptor alpha (PDGFRA) marks cMSCs, and demonstrates their epicardial location during embryogenesis. Over 100 clinical trials are currently using MSCs, however their natural role/s remain largely unknown, as are genes required for their development and maintenance. Aims To determine the role of PDGFRA in cMSC development. Methods Mouse embryos were genetically modified to express either no, or low levels of PDGFRA in the epicardium, or to express a long-lived fluorescent protein (GFP) from Pdgfra in order to trace progeny of PDGFRA-expressing cells. Embryos were analysed by confocal immunofluorescence microscopy and flow cytometry. cMSCs were quantified by colony forming assays. Results Three classes of epicardial-derived cells were identified with varying Pdgfra-GFP, PDGFRA and PDGFRB expression. Mice mutant for Pdgfra were deficient in two of these populations, and in cMSCs. Pdgfra-GFP was traced into coronary smooth muscle cells. Conclusions PDGFRA is essential for cMSC development. The data supports cMSC as progenitors for coronary smooth muscle.