P595PDGFRalpha demarcates the cardiogenic and clonogenic Sca-1+ stem cell

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Abstract

Cardiac progenitor/stem cells in adult hearts are a potential mode of self-repair, therapeutic product, and target for activation in situ, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, we define four sub-populations in adult mouse myocardium sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, platelet/endothelial cell adhesion molecule 1 (CD31), and platelet derived growth factor receptor-α (PDGFRα). SP status predicted clonogenicity plus cardiogenic genes' expression (Gata4/6, Hand2, Tbx5/20), properties segregating more specifically to PDGFRα+ cells. PDGFRα- cells were characterized, instead, by Kdr/Flk1, Cdh5, CD31 and lack of clone formation. Clonal progeny of single Sca1+ SP cells showed tri-lineage potential (cardiomyocyte, endothelial, smooth muscle) after cardiac grafting. By fate-mapping, PDGFRα+ CD31- cells derived from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα- CD31+ cells (Gata5, Wt1 low; Flk1, Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca-1+ stem cell.

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