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Tumour resistance in induced pluripotent stem cells derived from naked mole-rats

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Title: Tumour resistance in induced pluripotent stem cells derived from naked mole-rats
Authors: Miyawaki, Shingo Browse this author
Kawamura, Yoshimi Browse this author
Oiwa, Yuki Browse this author
Shimizu, Atsushi Browse this author
Hachiya, Tsuyoshi Browse this author
Bono, Hidemasa Browse this author →KAKEN DB
Koya, Ikuko Browse this author
Okada, Yohei Browse this author →KAKEN DB
Kimura, Tokuhiro Browse this author →KAKEN DB
Tsuchiya, Yoshihiro Browse this author
Suzuki, Sadafumi Browse this author →KAKEN DB
Onishi, Nobuyuki Browse this author →KAKEN DB
Kuzumaki, Naoko Browse this author →KAKEN DB
Matsuzaki, Yumi Browse this author
Narita, Minoru Browse this author →KAKEN DB
Ikeda, Eiji Browse this author →KAKEN DB
Okanoya, Kazuo Browse this author →KAKEN DB
Seino, Ken-ichiro Browse this author →KAKEN DB
Saya, Hideyuki Browse this author →KAKEN DB
Okano, Hideyuki Browse this author →KAKEN DB
Miura, Kyoko Browse this author
Issue Date: 10-May-2016
Publisher: Nature Publishing Group
Journal Title: Nature communications
Volume: 7
Start Page: 11471
Publisher DOI: 10.1038/ncomms11471
Abstract: The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype-ARF suppression-induced senescence (ASIS)-that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/62277
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 三浦 恭子

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