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Cancer Sci. 2018 Sep;109(9):2641-2650. doi: 10.1111/cas.13731. Epub 2018 Aug 15.

Unveiling epigenetic regulation in cancer, aging, and rejuvenation with in vivo reprogramming technology.

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Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
AMED-CREST, AMED, Tokyo, Japan.
Division of Stem Cell Pathology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.


Reprogramming technology has enabled the fate conversion of terminally differentiated somatic cells into pluripotent stem cells or into another differentiated state. A dynamic reorganization of epigenetic regulation takes place during cellular reprogramming. Given that reprogramming does not require changes in the underlying genome, the technology can be used to actively modify epigenetic regulation. Although reprogramming has been investigated mostly at the cellular level in vitro, studies have reported that somatic cells are reprogrammable in multicellular organisms in vivo. In vivo reprogramming provides a potential strategy for regenerative medicine. Notably, recent studies using in vivo reprogramming technology to alter epigenetic regulation at organismal levels have revealed unappreciated epigenetic mechanisms in various biological phenomena, including cancer development, tissue regeneration, aging, and rejuvenation in mammals. Moreover, in vivo reprogramming technology can be applied to abrogate epigenetic aberrations associated with aging and cancer, which raises the possibility that the technology could provide a potential strategy to control the fate of detrimental cells such as senescent cells and cancer cells in vivo. Here, we review recent progress and future perspectives of in vivo reprogramming.


aging; cancer; cellular senescence; epigenetics; in vivo reprogramming; reprogramming technology

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