Numerous genetic aberrations have been revealed in induced pluripotent stem (iPS) cells, which are generated by genome reprogramming of somatic cells. This fact gave us a great surprise, because it has been fully believed that genome reprogramming is only due to the remodeling of the epigenome. In addition, these aberrations aroused serious concerns over the use of iPS cells in regenerative medicine as they can cause immunogenicity and tumorigenicity. In our project we aim to elucidate the relationship between mechanisms of epigenome remodeling and genome maintenance by clarifying the characteristics, origin and emergence timing of these mutations, and by understanding the molecular mechanisms underlying these abnormalities. Furthermore, we also aim to generate iPS cells with few mutations through controlling the genome reprogramming processes based on our findings.
Team Leader, Ryoko Araki
Representative Articles
- Araki R, Hoki Y, Suga T, Obara C, Sunayama M, Imadome K, Fujita M, Kamimura S, Nakamura M, Wakayama S, Nagy A, Wakayama T, Abe M. Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency. Nat Commun. 2020 Jan 10;11(1):197.
- Fujita M, Imadome K, Somasundaram V, Kawanishi M, Karasawa K, Wink DA. Metabolic characterization of aggressive breast cancer cells exhibiting invasive phenotype: impact of non-cytotoxic doses of 2-DG on diminishing invasiveness. BMC Cancer. 2020 Sep 29;20(1):929.
- Sugiura M, Kasama Y, Araki R, Hoki Y, Sunayama M, Uda M, Nakamura M, Ando S, Abe M. Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells. Stem Cell Reports. 2014 Jan 2;2(1):52-63.
- Araki R, Uda M, Hoki Y, Sunayama M, Nakamura M, Ando S, Sugiura M, Ideno H, Shimada A, Nifuji A, Abe M. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature. 2013 Feb 7;494(7435):100-4.
- Araki R, Fujimori A, Hamatani K, Mita K, Saito T, Mori M, Fukumura R, Morimyo M, Muto M, Itoh M, Tatsumi K, Abe M. Nonsense mutation at Tyr-4046 in the DNA- dependent protein kinase catalytic subunit of severe combined immune deficiency mice. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2438-43.