Back

Title	en Tumour resistance in induced pluripotent stem cells derived from naked mole-rats
Creator	en Miyawaki, Shingo en Kawamura, Yoshimi en Oiwa, Yuki en Shimizu, Atsushi en Hachiya, Tsuyoshi en Bono, Hidemasa NRID 1000020364789 en Koya, Ikuko en Okada, Yohei NRID 1000030383714 en Kimura, Tokuhiro NRID 1000040445200 en Tsuchiya, Yoshihiro en Suzuki, Sadafumi NRID 1000070465003 en Onishi, Nobuyuki NRID 1000040534540 en Kuzumaki, Naoko NRID 1000010507669 en Matsuzaki, Yumi en Narita, Minoru NRID 1000040318613 en Ikeda, Eiji NRID 1000030232177 en Okanoya, Kazuo NRID 1000030211121 en Seino, Ken-ichiro NRID 1000020312845 en Saya, Hideyuki NRID 1000080264282 en Okano, Hideyuki NRID 1000060160694 en Miura, Kyoko
Accessrights	open access
Rights	https://creativecommons.org/licenses/by/4.0/ en Creative Commons Attribution 4.0 International
Subject	NDC 490
Description	Abstract en 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.
Publisher	en Nature Publishing Group
Date	Issued2016-05-10
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/62277
Relation	isIdenticalTo DOI https://doi.org/10.1038/ncomms11471
Journal	PISSN 2041-1723 NCID AA12645905 en Nature communications Volume Number7 Page Start11471
File	fulltext ncomms11471-s1.pdf 15.09 MB (application/pdf) Issued2016-05-10 fulltext ncomms11471.pdf 2.54 MB (application/pdf) Issued2016-05-10
Oaidate	2023-07-26