A Comparison of Senescence in Mouse and Human Cells

Gorbunova, Vera; Seluanov, Andrei

doi:10.1007/978-1-4419-1075-2_7

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“…An ideal balance between p53 and Rb activities may vary between different species of mammals. For example, mouse cells are known to rely more heavily on p53 while human cells rely more on Rb ( Gorbunova and Seluanov, 2010 , Li et al., 2009 ). This may reflect the choice between reliance on elimination of damaged cells by apoptosis in the case of activating p53 versus reliance on cell-cycle arrest and heterochromatin repressive functions in the case of Rb.…”

Section: Discussionmentioning

confidence: 99%

Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming

Tan

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et al. 2017

Stem Cell Reports

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SummaryNaked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming. Analysis of the global histone landscape revealed that NMR had higher levels of repressive H3K27 methylation marks and lower levels of activating H3K27 acetylation marks than mouse. ATAC-seq revealed that in NMR, promoters of reprogramming genes were more closed than mouse promoters, while expression of LT led to massive opening of the NMR promoters. These results suggest that NMR displays a more stable epigenome that resists de-differentiation, contributing to the cancer resistance and longevity of this species.

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Section: Discussionmentioning

confidence: 99%