title: Mouse SCNT ESCs have lower somatic mutation load than syngeneic iPSCs.
abstract: Ectopic expression of reprogramming factors has been widely adopted to reprogram somatic nucleus into a pluripotent state (induced pluripotent stem cells [iPSCs]). However, genetic aberrations such as somatic gene mutation in the resulting iPSCs have raised concerns regarding their clinical utility. To test whether the increased somatic mutations are primarily the by-products of current reprogramming methods, we reprogrammed embryonic fibroblasts of inbred C57BL/6 mice into either iPSCs (8 lines, 4 previously published) or embryonic stem cells (ESCs) with somatic cell nuclear transfer (SCNT ESCs; 11 lines). Exome sequencing of these lines indicates a significantly lower mutation load in SCNT ESCs than iPSCs of syngeneic background. In addition, one SCNT-ESC line has no detectable exome mutation, and two pairs of SCNT-ESC lines only have shared preexisting mutations. In contrast, every iPSC line carries unique mutations. Our study highlights the need for improving reprogramming methods in more physiologically relevant conditions.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA ; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lu
authors.affiliation: College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yong
authors.affiliation: Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
authors.affiliation: Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D053652:Nuclear Transfer Techniques; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
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