Induced Pluripotent Stem Cells from Cancer-Resistant Naked Mole-Rats

Stem cells play essential roles in the development and tissue homeostasis of animals and are closely associated with carcinogenesis and aging. Also, the somatic cell reprogramming process to induced pluripotent stem (iPS) cells shares several characteristics with carcinogenesis. In this chapter, we focus on iPS cells and the reprogramming process of somatic cells in the naked mole-rat (NMR), the longest-living rodent with remarkable cancer resistance capabilities. NMR somatic cells show resistance to reprogramming induction, and generated NMR-iPS cells have a unique tumor-resistant phenotype. This phenotype is regulated by expressional activation of the tumor suppressor ARF gene and loss-of-function mutation in oncogene ERAS. Notably, it was also found that NMR somatic cells undergo senescence when ARF is suppressed during reprogramming, which would contribute to the resistance to both reprogramming and cancer in NMR somatic cells. Further studies on reprogramming resistance in NMR somatic cells and their concomitant tumor resistance in NMR-iPS cells would contribute to a better understanding of both cancer resistance and delayed aging in NMRs. In addition, NMR-iPS cells can be used as a new and important cell source for advancing research concerning several extraordinary physiological characteristics of NMR. Furthermore, study of NMR-iPS cells could lead to the development of safer regenerative therapies in the future.