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Whole-genome mutational burden analysis of three pluripotency induction methods

Author

Listed:
  • Kunal Bhutani

    (Scripps Translational Science Institute and The Scripps Research Institute
    Present address: J. Craig Venter Institute, La Jolla, California 92037, USA)

  • Kristopher L. Nazor

    (The Scripps Research Institute, Center for Regenerative Medicine)

  • Roy Williams

    (The Scripps Research Institute, Center for Regenerative Medicine)

  • Ha Tran

    (The Scripps Research Institute, Center for Regenerative Medicine)

  • Heng Dai

    (BioNano Genomics
    Present address: WuXi NextCODE Genomics, Shanghai, China 200131)

  • Željko Džakula

    (BioNano Genomics)

  • Edward H. Cho

    (BioNano Genomics)

  • Andy W. C. Pang

    (BioNano Genomics)

  • Mahendra Rao

    (The National Institutes of Health
    Present address: New York Stem Cell Foundation, New York City, New York 10023 USA)

  • Han Cao

    (BioNano Genomics)

  • Nicholas J. Schork

    (Scripps Translational Science Institute and The Scripps Research Institute
    Present address: J. Craig Venter Institute, La Jolla, California 92037, USA)

  • Jeanne F. Loring

    (The Scripps Research Institute, Center for Regenerative Medicine)

Abstract

There is concern that the stresses of inducing pluripotency may lead to deleterious DNA mutations in induced pluripotent stem cell (iPSC) lines, which would compromise their use for cell therapies. Here we report comparative genomic analysis of nine isogenic iPSC lines generated using three reprogramming methods: integrating retroviral vectors, non-integrating Sendai virus and synthetic mRNAs. We used whole-genome sequencing and de novo genome mapping to identify single-nucleotide variants, insertions and deletions, and structural variants. Our results show a moderate number of variants in the iPSCs that were not evident in the parental fibroblasts, which may result from reprogramming. There were only small differences in the total numbers and types of variants among different reprogramming methods. Most importantly, a thorough genomic analysis showed that the variants were generally benign. We conclude that the process of reprogramming is unlikely to introduce variants that would make the cells inappropriate for therapy.

Suggested Citation

  • Kunal Bhutani & Kristopher L. Nazor & Roy Williams & Ha Tran & Heng Dai & Željko Džakula & Edward H. Cho & Andy W. C. Pang & Mahendra Rao & Han Cao & Nicholas J. Schork & Jeanne F. Loring, 2016. "Whole-genome mutational burden analysis of three pluripotency induction methods," Nature Communications, Nature, vol. 7(1), pages 1-8, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10536
    DOI: 10.1038/ncomms10536
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    Cited by:

    1. Ryoko Araki & Tomo Suga & Yuko Hoki & Kaori Imadome & Misato Sunayama & Satoshi Kamimura & Mayumi Fujita & Masumi Abe, 2024. "iPS cell generation-associated point mutations include many C > T substitutions via different cytosine modification mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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