Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency

Autor: Araki, Ryoko, Hoki, Yuko, Suga, Tomo, Obara, Chizuka, Sunayama, Misato, Imadome, Kaori, Fujita, Mayumi, Kamimura, Satoshi, Nakamura, Miki, Wakayama, Sayaka, Nagy, Andras, Wakayama, Teruhiko, Abe, Masumi, Ryoko, Araki, Yuko, Fujimori, Tomo, Suga, Chizuka, Obara, Misato, Sunayama, Kaori, Imadome, Mayumi, Fujita, Satoshi, Kamimura, Masumi, Abe
Jazyk: angličtina
Rok vydání: 2020
Zdroj: Nature communications. 11(1):197
ISSN: 2041-1723
Popis: A number of point mutations have been identified in reprogrammed pluripotent stem cells such as iPSCs and ntESCs. The molecular basis for these mutations has remained elusive however, which is a considerable impediment to their potential medical application. Here we report a specific stage at which iPSC generation is not reduced in response to ionizing radiation, i.e. radio-resistance. Quite intriguingly, a G1/S cell cycle checkpoint deficiency occurs in a transient fashion at the initial stage of the genome reprogramming process. These cancer-like phenomena, i.e. a cell cycle checkpoint deficiency resulting in the accumulation of point mutations, suggest a common developmental pathway between iPSC generation and tumorigenesis. This notion is supported by the identification of specific cancer mutational signatures in these cells. We describe efficient generation of human integration-free iPSCs using erythroblast cells, which have only a small number of point mutations and INDELs, none of which are in coding regions.
Databáze: OpenAIRE