PDGFR alpha demarcates the cardiogenic clonogenic Sca1(+) stem/progenitor cell in adult murine myocardium

Abstract

Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT–PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-a (PDGFRa) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRaþ cells. Clonal progeny of single Sca1þ SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRa cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRaþ/CD31 cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRa /CD31þ cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRa demarcates the clonogenic cardiogenic Sca1þ stem/progenitor cell.