Department of Biology, University of Rochester, Rochester, NY 14627, USA; Laboratory of Epigenetics, Institutes of Biomedical Sciences and Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, P. R. China.
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Stem Cell Reports. 2017 Nov 14;9(5):1721-1734. doi: 10.1016/j.stemcr.2017.10.001. Epub 2017 Oct 26.
Naked 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.
裸鼹鼠（NMR）由于其异常的长寿和抗癌能力，是衰老和癌症研究的有价值模型。我们观察到，NMR 成纤维细胞对 OSKM 的重编程效率远低于小鼠成纤维细胞。SV40 大 T 抗原（LT）的表达显著提高了 NMR 成纤维细胞的重编程效率。单独失活 Rb，但不失活 p53，足以提高重编程效率，这表明 NMR 染色质可能难以重编程。对全局组蛋白景观的分析表明，NMR 具有比小鼠更高水平的抑制性 H3K27 甲基化标记和更低水平的激活 H3K27 乙酰化标记。ATAC-seq 显示，在 NMR 中，重编程基因的启动子比小鼠的启动子更封闭，而 LT 的表达导致大量 NMR 启动子开放。这些结果表明，NMR 显示出更稳定的表观基因组，抵抗去分化，这有助于该物种的抗癌和长寿。
