Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression

Linzhao Cheng, Nancy F. Hansen, Ling Zhao, Yutao Du, Chunlin Zou, Frank X. Donovan, Bin Kuan Chou, Guangyu Zhou, Shijie Li, Sarah N. Dowey, Zhaohui Ye, Settara C. Chandrasekharappa, Huanming Yang, James C. Mullikin, P. Paul Liu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)337-344
Number of pages8
JournalCell stem cell
Volume10
Issue number3
DOIs
StatePublished - Mar 2 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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