Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming
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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.
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DNA methylation tends to increase with age at some CpG islands, particularly at polycomb target genes and at promoters of tumour suppressor genes.
“DNA methylation tends to increase with age at some CpG islands, particularly at polycomb target genes 55,56 and at promoters of tumour suppressor genes 57 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [56]
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- Authors
- Tan, L., Ke, Z., Tombline, G., Macoretta, N., Hayes, K., Tian, X., Lv, R., Ablaeva, J., Gilbert, M., Bhanu, N. V., Yuan, Z.-F., Garcia, B. A., Shi, Y. G., Shi, Y., Seluanov, A., & Gorbunova, V.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- University of Rochester (US)
- University of Pennsylvania (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Seluanov, Andrei
- Gorbunova, Vera
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 9
- Issue
- 5
- Pages
- 1721-1734
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC5831052
- OpenAlex
- W2766533987
- Cited by
- 88
- References
- 50
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 16 · 2022: 12 · 2021: 19 · 2020: 8 · 2019: 12 · 2018: 7 · 2017: 1
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (GM110174, CA196539, AG047200, AG027237, AG051449, AG046320)
- Life Extension Foundation
- NSFC (31200966)
- Shanghai Pujiang Talent Program (16PJ1401500)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- naked mole-rat, induced pluripotent stem cell reprogramming, OSKM, SV40 large T antigen, Rb inactivation, p53, H3K27 methylation, H3K27 acetylation, promoter accessibility, chromatin accessibility, fibroblasts, tumor resistance, longevity, aging
- MeSH terms
- Animals, Antigens, Polyomavirus Transforming, Chimera, Chromatin, Fibroblasts, Genome, Mole Rats, Animals, Genetically Modified, Histone Code, Epigenesis, Genetic, Mice, Induced Pluripotent Stem Cells, Cellular Reprogramming
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