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

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 adu...

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Detalles Bibliográficos
Autores principales: Noseda, Michela, Harada, Mutsuo, McSweeney, Sara, Leja, Thomas, Belian, Elisa, Stuckey, Daniel J., Abreu Paiva, Marta S., Habib, Josef, Macaulay, Iain, de Smith, Adam J., al-Beidh, Farah, Sampson, Robert, Lumbers, R. Thomas, Rao, Pulivarthi, Harding, Sian E., Blakemore, Alexandra I. F., Eirik Jacobsen, Sten, Barahona, Mauricio, Schneider, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479024/
https://www.ncbi.nlm.nih.gov/pubmed/25980517
http://dx.doi.org/10.1038/ncomms7930
Descripción
Sumario: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.