IPS Cell Generation-associated Point Mutations Include Many C > T Substitutions Via Different Cytosine Modification Mechanisms

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 11

PMID 38862540

Authors

Ryoko Araki

Tomo Suga

Yuko Hoki

Kaori Imadome

Misato Sunayama

Satoshi Kamimura

Mayumi Fujita

Masumi Abe

Affiliations

Soon will be listed here.

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.

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