title: Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression.
abstract: The utility of induced pluripotent stem cells (iPSCs) as models to study diseases and as sources for cell therapy depends on the integrity of their genomes. Despite recent publications of DNA sequence variations in the iPSCs, the true scope of such changes for the entire genome is not clear. Here we report the whole-genome sequencing of three human iPSC lines derived from two cell types of an adult donor by episomal vectors. The vector sequence was undetectable in the deeply sequenced iPSC lines. We identified 1,058-1,808 heterozygous single-nucleotide variants (SNVs), but no copy-number variants, in each iPSC line. Six to twelve of these SNVs were within coding regions in each iPSC line, but ~50% of them are synonymous changes and the remaining are not selectively enriched for known genes associated with cancers. Our data thus suggest that episome-mediated reprogramming is not inherently mutagenic during integration-free iPSC induction.
authors.affiliation: Stem Cell Program in Institute for Cell Engineering and Division of Hematology, Johns Hopkins University, Baltimore, MD 21205, USA. lcheng@welch.jhu.edu
authors.forename: Linzhao
authors.initials: L
authors.lastname: Cheng
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Hansen
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Yutao
authors.initials: Y
authors.lastname: Du
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zou
authors.forename: Frank X
authors.initials: FX
authors.lastname: Donovan
authors.forename: Bin-Kuan
authors.initials: BK
authors.lastname: Chou
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhou
authors.forename: Shijie
authors.initials: S
authors.lastname: Li
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Dowey
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ye
authors.forename: Settara C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.forename: P Paul
authors.initials: PP
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics; D014644:Genetic Variation; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D007963:Leukocytes, Mononuclear; D046228:Microarray Analysis; D010957:Plasmids / Q000235:genetics*; D017422:Sequence Analysis, DNA