Unique features of mutations revealed by sequentially reprogrammed induced pluripotent stem cells

Shuai Gao, Caihong Zheng, Gang Chang, Wenqiang Liu, Xiaochen Kou, Kun Tan, Li Tao, Kai Xu, Hong Wang, Jun Cai (), Jianhui Tian () and Shaorong Gao ()
Additional contact information
Shuai Gao: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction
Caihong Zheng: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics
Gang Chang: National Institute of Biological Sciences, NIBS
Wenqiang Liu: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University
Xiaochen Kou: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University
Kun Tan: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction
Li Tao: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction
Kai Xu: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University
Hong Wang: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University
Jun Cai: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics
Jianhui Tian: Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction
Shaorong Gao: National Institute of Biological Sciences, NIBS

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms7318 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7318

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7318

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().