PT  - JOURNAL ARTICLE
AU  - Kathleen Broughton
AU  - Tiffany Khieu
AU  - Nicky Nguyen
AU  - Michael Rosa
AU  - Sadia Mohsin
AU  - Pearl Quijada
AU  - Jessica Wang
AU  - Oscar Echeagaray
AU  - Dieter Kubli
AU  - Taeyong Kim
AU  - Fareheh Firouzi
AU  - Megan Monsanto
AU  - Natalie Gude
AU  - Robert M. Adamson
AU  - Walter P. Dembitsky
AU  - Michael Davis
AU  - Mark A. Sussman
TI  - Tetraploidy in rodent cardiac stem cells confers enhanced biological properties
AID  - 10.1101/521716
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 521716
4099  - http://biorxiv.org/content/early/2019/01/16/521716.short
4100  - http://biorxiv.org/content/early/2019/01/16/521716.full
AB  - Ploidy for cardiomyocytes is well described but remains obscure in cardiac interstitial cells (CICs). Ploidy of c-kit+CICs were assessed using a combination of confocal, karyotypic, and flow cytometric assessments coupled with molecular and bioinformatic analyses. Fundamental differences were found between cultured rodent (rat, mouse) c-kit+CICs possessing mononuclear tetraploid (4n) content versus large mammal (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in c-kit+CICs from human and a mixture of diploid and tetraploid nuclei in mouse. Molecular assessment of the p53 signaling pathway provides a plausible explanation for escape from replicative senescence in rodent but not human ckit+CICs. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse ckit+CICs, alluding to functional divergences. Collectively, these data reveal fundamental species-specific biological differences in c-kit+CICs that could account for challenges in extrapolation of myocardial preclinical studies from rodent to large animal models.