RRC ID 80963
Author Araki R, Suga T, Hoki Y, Imadome K, Sunayama M, Kamimura S, Fujita M, Abe M.
Title iPS cell generation-associated point mutations include many C > T substitutions via different cytosine modification mechanisms.
Journal Nat Commun
Abstract Genomic aberrations are a critical impediment for the safe medical use of iPSCs and their origin and developmental mechanisms remain unknown. Here we find through WGS analysis of human and mouse iPSC lines that genomic mutations are de novo events and that, in addition to unmodified cytosine base prone to deamination, the DNA methylation sequence CpG represents a significant mutation-prone site. CGI and TSS regions show increased mutations in iPSCs and elevated mutations are observed in retrotransposons, especially in the AluY subfamily. Furthermore, increased cytosine to thymine mutations are observed in differentially methylated regions. These results indicate that in addition to deamination of cytosine, demethylation of methylated cytosine, which plays a central role in genome reprogramming, may act mutagenically during iPSC generation.
Volume 15(1)
Pages 4946
Published 2024-6-11
DOI 10.1038/s41467-024-49335-5
PII 10.1038/s41467-024-49335-5
PMID 38862540
PMC PMC11166658
MeSH Animals Cell Line Cellular Reprogramming / genetics CpG Islands* Cytosine* / metabolism DNA Methylation* Humans Induced Pluripotent Stem Cells* / metabolism Mice Point Mutation* Retroelements / genetics
Resource
Mice RBRC02290