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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-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression ( Gata4/6 ,  Hand2  and  Tbx5/20 ), properties segregating more specifically to PDGFRα +  cells. Clonal progeny of single Sca1 +  SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα −  cells are characterized by  Kdr/Flk1 ,  Cdh5 , CD31 and lack of clonogenicity. PDGFRα + /CD31 −  cells derive from cells formerly expressing  Mesp1 ,  Nkx2-5 ,  Isl1 ,  Gata5  and  Wt1 , distinct from PDGFRα − /CD31 +  cells ( Gata5  low;  Flk1  and  Tie2  high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1 +  stem/progenitor cell.

PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium