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

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Listed:
  • Michela Noseda

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Mutsuo Harada

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Sara McSweeney

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Thomas Leja

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Elisa Belian

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Daniel J. Stuckey

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London
    Centre for Advanced Biomedical Imaging (CABI), University College London)

  • Marta S. Abreu Paiva

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Josef Habib

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London
    King’s College London)

  • Iain Macaulay

    (Haematopoietic Stem Cell Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford)

  • Adam J. de Smith

    (Imperial College London
    University of California, San Francisco)

  • Farah al-Beidh

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Robert Sampson

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • R. Thomas Lumbers

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Pulivarthi Rao

    (Texas Children’s Cancer Center, Baylor College of Medicine
    Baylor College of Medicine)

  • Sian E. Harding

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, 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
    Imperial College London)

  • Michael D. Schneider

    (British Heart Foundation Centre of Research Excellence, Imperial College London
    National Heart and Lung Institute, Imperial College London)

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.

Suggested Citation

  • 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 Samps, 2015. "PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium," Nature Communications, Nature, vol. 6(1), pages 1-16, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7930
    DOI: 10.1038/ncomms7930
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    Cited by:

    1. Fabian Peisker & Maurice Halder & James Nagai & Susanne Ziegler & Nadine Kaesler & Konrad Hoeft & Ronghui Li & Eric M. J. Bindels & Christoph Kuppe & Julia Moellmann & Michael Lehrke & Christian Stopp, 2022. "Mapping the cardiac vascular niche in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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