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

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

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30 Citations (Scopus)

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.

Original languageEnglish
Article number11471
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 May 10

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Miyawaki, S., Kawamura, Y., Oiwa, Y., Shimizu, A., Hachiya, T., Bono, H., Koya, I., Okada, Y., Kimura, T., Tsuchiya, Y., Suzuki, S., Onishi, N., Kuzumaki, N., Matsuzaki, Y., Narita, M., Ikeda, E., Okanoya, K., Seino, K. I., Saya, H., ... Miura, K. (2016). Tumour resistance in induced pluripotent stem cells derived from naked mole-rats. Nature communications, 7, [11471]. https://doi.org/10.1038/ncomms11471