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

Nat Commun. 2015 May 18;6:6930. doi: 10.1038/ncomms7930.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxin-1 / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Differentiation
  • Cell Lineage
  • Endothelial Cells / cytology
  • Female
  • GATA4 Transcription Factor / genetics
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / metabolism*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Phenotype
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Principal Component Analysis
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Regeneration
  • Stem Cells / cytology*
  • T-Box Domain Proteins / genetics

Substances

  • Ataxin-1
  • Atxn1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • Hand2 protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Receptor, Platelet-Derived Growth Factor alpha