期刊
NATURE
卷 471, 期 7336, 页码 63-U76出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature09805
关键词
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资金
- NIH [R01 HL094963]
- UCSD
- California Institute for Regenerative Medicine [TG2-01154]
- CIRM [RC1-00116]
- Focht-Powell Fellowship
- National Institute of General Medical Sciences [T32 GM008666]
- A*Star Institute of Medical Biology
- Singapore Stem Cell Consortium
- MICINN
- Sanofi-Aventis
- G. Harold and Leila Y. Mathers Foundation
- Cellex Foundation
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.
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