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

作者: Michela Noseda , Mutsuo Harada , Sara McSweeney , Thomas Leja , Elisa Belian

DOI: 10.1038/NCOMMS7930

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

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