Lower genomic stability of induced pluripotent stem cells reflects increased non-homologous end joining

Cancer Communications

Huixian Liu¹  Yingli Sun¹  Zitong Zhao¹  Minjie Zhang¹  Caiyun Yang¹  Xiao Han¹  Duanqing Pei¹  Zilong Zhang¹  Xin Xie¹  Jun Cai¹  Ke An²  Fengxia Du³  Qi Zhou³  Liu Wang³  Guochao Li³  Yuan Long³ 

[1] Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, P. R. China;State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P. R. China;University of Chinese Academy of Sciences, Beijing, P. R. China

关键词: Genomic stability;    DNA damage repair;    iPSCs;    ESCs;   

DOI  :  10.1186/s40880-018-0313-0

学科分类：肿瘤学

来源: Springer

【 摘 要 】

Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) share many common features, including similar morphology, gene expression and in vitro differentiation profiles. However, genomic stability is much lower in iPSCs than in ESCs. In the current study, we examined whether changes in DNA damage repair in iPSCs are responsible for their greater tendency towards mutagenesis. Mouse iPSCs, ESCs and embryonic fibroblasts were exposed to ionizing radiation (4 Gy) to introduce double-strand DNA breaks. At 4 h later, fidelity of DNA damage repair was assessed using whole-genome re-sequencing. We also analyzed genomic stability in mice derived from iPSCs versus ESCs. In comparison to ESCs and embryonic fibroblasts, iPSCs had lower DNA damage repair capacity, more somatic mutations and short indels after irradiation. iPSCs showed greater non-homologous end joining DNA repair and less homologous recombination DNA repair. Mice derived from iPSCs had lower DNA damage repair capacity than ESC-derived mice as well as C57 control mice. The relatively low genomic stability of iPSCs and their high rate of tumorigenesis in vivo appear to be due, at least in part, to low fidelity of DNA damage repair.

【 授权许可】

CC BY