Somatic coding mutations in human induced pluripotent stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03

AUTHORS

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 Belmonte, Derrick J. Rossi, James A. Thomson, Kevin Eggan, George Q. Daley, Lawrence S. B. Goldstein, Kun Zhang

ABSTRACT

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. More... »

PAGES

63

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09805

    DOI

    http://dx.doi.org/10.1038/nature09805

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053576860

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21368825


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