RRC ID 58392
Author 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.
Title Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency.
Journal Nat Commun
Abstract 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.
Volume 11(1)
Pages 197
Published 2020-1-10
DOI 10.1038/s41467-019-13830-x
PII 10.1038/s41467-019-13830-x
PMID 31924765
PMC PMC6954237
MeSH Animals Cell Division Cellular Reprogramming Erythroblasts G1 Phase Cell Cycle Checkpoints / genetics* G1 Phase Cell Cycle Checkpoints / radiation effects Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism* Induced Pluripotent Stem Cells / radiation effects Neoplasms / genetics Open Reading Frames Point Mutation S Phase Cell Cycle Checkpoints / genetics* S Phase Cell Cycle Checkpoints / radiation effects X-Rays
IF 12.121
Times Cited 0
Mice RBRC02290
Human and Animal Cells Jurkat(RCB3052)