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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.

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


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.


Heart stem cells

Conflict of interest statement

Competing interestsThe authors declare no competing interests.

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