title: Unique features of mutations revealed by sequentially reprogrammed induced pluripotent stem cells.
abstract: Although viable mice can be generated from induced pluripotent stem cells (iPSCs), the impact of accumulated mutations on the developmental potential of the resulting iPSCs remains to be determined. Here, we demonstrate that all-iPSC mice generated through tetraploid blastocysts complementation can tolerate the accumulation of somatic mutations for up to six generations using a Tet-on inducible reprogramming system. But, the viability of the all-iPS mice decreased with increasing generations. A whole-genome sequencing survey revealed that thousands of single-nucleotide variations (SNVs), including 44 non-synonymous ones, accumulated throughout the sequential reprogramming process. Subsequent analysis provides evidence that these accumulated SNVs account for the gradual reduction in viability of the resultant all-iPSC mice. Unexpectedly, our present reprogramming system revealed that pluripotent stem cells are heterogeneous in terms of possessing a set of copy-number alterations (CNAs). These CNAs are unique for pluripotent cells and subsequently disappear in the differentiating progenies.
authors.affiliation: 1] Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction; National Engineering Laboratory for Animal Breeding; College of Animal Sciences and Technology, China Agricultural University, Beijing 100193, China [2] National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, CAS Beijing 100101, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing 102206, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity &Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity &Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Kou
authors.affiliation: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction; National Engineering Laboratory for Animal Breeding; College of Animal Sciences and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tan
authors.affiliation: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction; National Engineering Laboratory for Animal Breeding; College of Animal Sciences and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity &Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity &Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, CAS Beijing 100101, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction; National Engineering Laboratory for Animal Breeding; College of Animal Sciences and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Tian
authors.affiliation: 1] National Institute of Biological Sciences, NIBS, Beijing 102206, China [2] Clinical and Translational Research Center of Shanghai First Maternity &Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D003433:Crosses, Genetic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018628:Gene Dosage; D016678:Genome; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide