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

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 s...

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Published inNature communications Vol. 7; no. 1; pp. 11471 - 9
Main Authors 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 10.05.2016
Nature Publishing Group
Nature Portfolio
Subjects
13
38/91
631/136/532/2064/2158
631/67/581
692/308/2171
692/420/755
Animals
Cancer
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - immunology
Cellular Reprogramming - genetics
Cellular Reprogramming - immunology
Cloning
Gene expression
Genes, Tumor Suppressor
Humanities and Social Sciences
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - immunology
Induced Pluripotent Stem Cells - transplantation
Life sciences
Male
Medicine
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Nude
Mice, SCID
Mole Rats - genetics
Mole Rats - immunology
multidisciplinary
Mutation
Oncogene Protein p21(ras) - genetics
Oncogene Protein p21(ras) - immunology
Polymerase chain reaction
Reading Frames
Rodents
Science
Science (multidisciplinary)
Senescence
Stem cells
Teratoma - genetics
Teratoma - immunology
Testicular Neoplasms - genetics
Testicular Neoplasms - immunology
Tumors
Japan
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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. The naked mole-rat exhibits an exceptional resistance to cancer. Here, the authors show that induced pluripotent stem cells derived from the naked mole-rat lack teratoma-forming tumorigenicity due to a naked mole-rat-specific ARF-dependent tumour-suppression mechanism.
AbstractList 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. The naked mole-rat exhibits an exceptional resistance to cancer. Here, the authors show that induced pluripotent stem cells derived from the naked mole-rat lack teratoma-forming tumorigenicity due to a naked mole-rat-specific ARF-dependent tumour-suppression mechanism.
The naked mole-rat exhibits an exceptional resistance to cancer. Here, the authors show that induced pluripotent stem cells derived from the naked mole-rat lack teratoma-forming tumorigenicity due to a naked mole-rat-specific ARF-dependent tumour-suppression mechanism.
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.
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.
ArticleNumber 11471
Author Kuzumaki, Naoko
Ikeda, Eiji
Matsuzaki, Yumi
Kimura, Tokuhiro
Tsuchiya, Yoshihiro
Suzuki, Sadafumi
Saya, Hideyuki
Koya, Ikuko
Okada, Yohei
Hachiya, Tsuyoshi
Oiwa, Yuki
Onishi, Nobuyuki
Okanoya, Kazuo
Shimizu, Atsushi
Bono, Hidemasa
Kawamura, Yoshimi
Miura, Kyoko
Narita, Minoru
Seino, Ken-ichiro
Miyawaki, Shingo
Okano, Hideyuki
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27161380$$D View this record in MEDLINE/PubMed
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Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
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Snippet The naked mole-rat (NMR, Heterocephalus glaber ), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that...
The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that...
The naked mole-rat exhibits an exceptional resistance to cancer. Here, the authors show that induced pluripotent stem cells derived from the naked mole-rat...
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StartPage 11471
SubjectTerms 13
38/91
631/136/532/2064/2158
631/67/581
692/308/2171
692/420/755
Animals
Cancer
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - immunology
Cellular Reprogramming - genetics
Cellular Reprogramming - immunology
Cloning
Gene expression
Genes, Tumor Suppressor
Humanities and Social Sciences
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - immunology
Induced Pluripotent Stem Cells - transplantation
Life sciences
Male
Medicine
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Nude
Mice, SCID
Mole Rats - genetics
Mole Rats - immunology
multidisciplinary
Mutation
Oncogene Protein p21(ras) - genetics
Oncogene Protein p21(ras) - immunology
Polymerase chain reaction
Reading Frames
Rodents
Science
Science (multidisciplinary)
Senescence
Stem cells
Teratoma - genetics
Teratoma - immunology
Testicular Neoplasms - genetics
Testicular Neoplasms - immunology
Tumors
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Title Tumour resistance in induced pluripotent stem cells derived from naked mole-rats
URI https://link.springer.com/article/10.1038/ncomms11471
https://www.ncbi.nlm.nih.gov/pubmed/27161380
https://www.proquest.com/docview/1787795765
https://pubmed.ncbi.nlm.nih.gov/PMC4866046
https://doaj.org/article/4c96ca7ac9674011acb4f973f6e4f4db
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