Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals

Commun Biol. 2019 Jun 13;2:205. doi: 10.1038/s42003-019-0453-z. eCollection 2019.

Abstract

Cardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cardiac interstitial cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) c-kit+ cardiac interstitial cells possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in human c-kit+ cardiac interstitial cells and a mixture of diploid and tetraploid content in mouse. Downregulation of the p53 signaling pathway provides evidence why rodent, but not human, c-kit+ cardiac interstitial cells escape replicative senescence. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse c-kit+ cardiac interstitial cells, alluding to functional divergences. Collectively, these data reveal notable species-specific biological differences in c-kit+ cardiac interstitial cells, which could account for challenges in extrapolation of myocardial from preclinical studies to clinical trials.

Keywords: Heart stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cellular Senescence*
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Karyotyping
  • Leukocytes, Mononuclear / cytology
  • Male
  • Mice
  • Microscopy, Confocal
  • Myocytes, Cardiac / metabolism*
  • Ploidies
  • Rats
  • Signal Transduction*
  • Stem Cells / cytology*
  • Swine
  • Tetraploidy*