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

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

Author information

1
1San Diego State University Heart Institute and the Integrated Regenerative Research Institute, 5500 Campanile Drive, San Diego, CA 92182 USA.
2
2Cardiovascular Research Center, Temple University, 3500 N. Broad St., Philadelphia, 19140 PA USA.
3
3Division of Cardiology, Sharp Memorial Hospital, 8010 Frost St., San Diego, 92123 CA USA.
4
4Biomedical Engineering and Medicine, Emory University, 1760 Haygood Dr., Atlanta, 30322 GA USA.

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

Conflict of interest statement

Competing interestsThe authors declare no competing interests.

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