Open AccessDNA repair and replication links to pluripotency and differentiation capacity of pig iPS cells
Author(s) -
Kai Liu,
Jian Mao,
Liguo Song,
Anran Fan,
Sheng Zhang,
Yunlong Wang,
Nana Fan,
Na Liu,
Xiaoying Ye,
Haifeng Fu,
Zhongli Zhou,
Yong Wang,
Hong Wei,
Liu Z,
Ziyi Li,
Liangxue Lai,
Xumin Wang,
Lin Liu
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0173047
Subject(s) - induced pluripotent stem cell , biology , wnt signaling pathway , microbiology and biotechnology , embryonic stem cell , stem cell , cellular differentiation , dna repair , genetics , signal transduction , gene
Pigs are proposed to be suitable large animal models for test of the efficacy and safety of induced pluripotent stem cells (iPSCs) for stem cell therapy, but authentic pig ES/iPS cell lines with germline competence are rarely produced. The pathways or signaling underlying the defective competent pig iPSCs remain poorly understood. By improving induction conditions using various small chemicals, we generated pig iPSCs that exhibited high pluripotency and differentiation capacity that can contribute to chimeras. However, their potency was reduced with increasing passages by teratoma formation test, and correlated with declined expression levels of Rex1 , an important marker for naïve state. By RNA-sequencing analysis, genes related to WNT signaling were upregulated and MAPK signaling and TGFβ pathways downregulated in pig iPSCs compared to fibroblasts, but they were abnormally expressed during passages. Notably, pathways involving in DNA repair and replication were upregulated at early passage, but downregulated in iPSCs during prolonged passage in cluster with fibroblasts. Our data suggests that reduced DNA repair and replication capacity links to the instability of pig iPSCs. Targeting these pathways may facilitate generation of truly pluripotent pig iPSCs, with implication in translational studies.