PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell in adult murine myocardium, which augments cardiac function after grafting despite rare durable engraftment.
PDGFRα expression identifies a specific subpopulation of clonogenic and cardiogenic Sca1+ stem/progenitor cells in the adult mouse heart, providing a refined target for cardiac regeneration research.
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.
Noseda et al. (2015) studied Myocardial regeneration (murine model). PDGFRα+ Sca1+ cell grafting vs. Vehicle control was evaluated. PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell in adult murine myocardium, which augments cardiac function after grafting despite rare durable engraftment.