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

Miyawaki, Shingo  ,  Kawamura, Yoshimi  ,  Oiwa, Yuki  ,  Shimizu, Atsushi  ,  Hachiya, Tsuyoshi  ,  Bono, Hidemasa  ,  Koya, Ikuko  ,  Okada, Yohei  ,  Kimura, Tokuhiro  ,  Tsuchiya, Yoshihiro  ,  Suzuki, Sadafumi  ,  Onishi, Nobuyuki  ,  Kuzumaki, Naoko  ,  Matsuzaki, Yumi  ,  Narita, Minoru  ,  Ikeda, Eiji  ,  Okanoya, Kazuo  ,  Seino, Ken-ichiro  ,  Saya, Hideyuki  ,  Okano, Hideyuki  ,  Miura, Kyoko

7p.11471 , 2016-05-10 , Nature Publishing Group
ISSN:2041-1723
NCID:AA12645905
Description
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.
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http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/62277/1/ncomms11471.pdf

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