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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 Cells Have a Stable Epigenome that Resists iPSC Reprogramming.

Author information

1
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.
2
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
3
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.
4
Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
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; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
6
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; Division of Newborn Medicine, Boston Children's Hospital, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
7
Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: andrei.seluanov@rochester.edu.
8
Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: vera.gorbunova@rochester.edu.

Abstract

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.

KEYWORDS:

epigenome; iPS cells; naked mole rat

PMID:
29107597
PMCID:
PMC5831052
DOI:
10.1016/j.stemcr.2017.10.001
[Indexed for MEDLINE]
Free PMC Article

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