Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency.
Nat Commun
; 11(1): 197, 2020 01 10.
Article
in En
| MEDLINE
| ID: mdl-31924765
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Induced Pluripotent Stem Cells
/
G1 Phase Cell Cycle Checkpoints
/
S Phase Cell Cycle Checkpoints
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2020
Document type:
Article
Affiliation country:
Japón