Somatic coding mutations in human induced pluripotent stem cells

Athurva Gore, Zhe Li, Ho Lim Fung, Jessica E. Young, Suneet Agarwal, Jessica Antosiewicz-Bourget, Isabel Canto, Alessandra Giorgetti, Mason A. Israel, Evangelos Kiskinis, Je Hyuk Lee, Yuin Han Loh, Philip D. Manos, Nuria Montserrat, Athanasia D. Panopoulos, Sergio Ruiz, Melissa L. Wilbert, Junying Yu, Ewen F. Kirkness, Juan Carlos Izpisua BelmonteDerrick J. Rossi, James A. Thomson, Kevin Eggan, George Q. Daley, Lawrence S B Goldstein, Kun Zhang

Research output: Contribution to journalArticlepeer-review

1039 Scopus citations


Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.

Original languageEnglish (US)
Pages (from-to)63-67
Number of pages5
Issue number7336
StatePublished - Mar 3 2011

ASJC Scopus subject areas

  • General


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