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

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Authors

External Institution(s)

  • San Diego State University
  • Sharp Healthcare
  • Emory University

Details

Original languageEnglish (US)
Article number205
JournalCommunications Biology
Volume2
Issue number1
StatusPublished - Dec 1 2019
Peer-reviewedYes

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.

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Broughton, KM, Khieu, T, Nguyen, N, Rosa, M, Mohsin, S, Quijada, P, Wang, BJ, Echeagaray, OH, Kubli, DA, Kim, T, Firouzi, F, Monsanto, MM, Gude, NA, Adamson, RM, Dembitsky, WP, Davis, ME & Sussman, MA 2019, 'Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals', Communications Biology, vol. 2, no. 1, 205. https://doi.org/10.1038/s42003-019-0453-z