title: DNA repair and replication links to pluripotency and differentiation capacity of pig iPS cells.
abstract: 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.
authors.affiliation: Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.affiliation: Beijing Institute of Genomics, Chinese academy of Sciences, Beijing, China.
authors.forename: Lipu
authors.initials: L
authors.lastname: Song
authors.affiliation: First Hospital, Jilin University, Changchun, China.
authors.forename: Anran
authors.initials: A
authors.lastname: Fan
authors.affiliation: First Hospital, Jilin University, Changchun, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: First Hospital, Jilin University, Changchun, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Lai
authors.affiliation: Beijing Institute of Genomics, Chinese academy of Sciences, Beijing, China.
authors.forename: Xumin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004260:DNA Repair; D004261:DNA Replication; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D020935:MAP Kinase Signaling System; D051379:Mice; D013552:Swine