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

Michela Noseda (), Mutsuo Harada, Sara McSweeney, Thomas Leja, Elisa Belian, Daniel J. Stuckey, Marta S. Abreu Paiva, Josef Habib, Iain Macaulay, Adam J. de Smith, Farah al-Beidh, Robert Sampson, R. Thomas Lumbers, Pulivarthi Rao, Sian E. Harding, Alexandra I. F. Blakemore, Sten Eirik Jacobsen, Mauricio Barahona and Michael D. Schneider ()
Additional contact information
Michela Noseda: British Heart Foundation Centre of Research Excellence, Imperial College London
Mutsuo Harada: British Heart Foundation Centre of Research Excellence, Imperial College London
Sara McSweeney: British Heart Foundation Centre of Research Excellence, Imperial College London
Thomas Leja: British Heart Foundation Centre of Research Excellence, Imperial College London
Elisa Belian: British Heart Foundation Centre of Research Excellence, Imperial College London
Daniel J. Stuckey: British Heart Foundation Centre of Research Excellence, Imperial College London
Marta S. Abreu Paiva: British Heart Foundation Centre of Research Excellence, Imperial College London
Josef Habib: British Heart Foundation Centre of Research Excellence, Imperial College London
Iain Macaulay: Haematopoietic Stem Cell Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford
Adam J. de Smith: Imperial College London
Farah al-Beidh: British Heart Foundation Centre of Research Excellence, Imperial College London
Robert Sampson: British Heart Foundation Centre of Research Excellence, Imperial College London
R. Thomas Lumbers: British Heart Foundation Centre of Research Excellence, Imperial College London
Pulivarthi Rao: Texas Children’s Cancer Center, Baylor College of Medicine
Sian E. Harding: British Heart Foundation Centre of Research Excellence, Imperial College London
Alexandra I. F. Blakemore: Imperial College London
Sten Eirik Jacobsen: Haematopoietic Stem Cell Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford
Mauricio Barahona: British Heart Foundation Centre of Research Excellence, Imperial College London
Michael D. Schneider: British Heart Foundation Centre of Research Excellence, Imperial College London

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms7930

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