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

Research output: Contribution to journalArticle


External Institution(s)

  • San Diego State University
  • Sharp Healthcare
  • Emory University


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


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.

Citation formats



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.