Resident c-kit(+) cells in the heart are not cardiac stem cells

Nat Commun. 2015 Oct 30;6:8701. doi: 10.1038/ncomms9701.

Abstract

Identifying a bona fide population of cardiac stem cells (CSCs) is a critical step for developing cell-based therapies for heart failure patients. Previously, cardiac c-kit(+) cells were reported to be CSCs with a potential to become myocardial, endothelial and smooth muscle cells in vitro and after cardiac injury. Here we provide further insights into the nature of cardiac c-kit(+) cells. By targeting the c-kit locus with multiple reporter genes in mice, we find that c-kit expression rarely co-localizes with the expression of the cardiac progenitor and myogenic marker Nkx2.5, or that of the myocardial marker, cardiac troponin T (cTnT). Instead, c-kit predominantly labels a cardiac endothelial cell population in developing and adult hearts. After acute cardiac injury, c-kit(+) cells retain their endothelial identity and do not become myogenic progenitors or cardiomyocytes. Thus, our work strongly suggests that c-kit(+) cells in the murine heart are endothelial cells and not CSCs.

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Female
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / metabolism

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Nkx2-5 protein, mouse
  • Transcription Factors
  • Proto-Oncogene Proteins c-kit