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Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming

Author

Listed:
  • Sergio Ruiz

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Athurva Gore

    (University of California at San Diego)

  • Zhe Li

    (University of California at San Diego)

  • Athanasia D. Panopoulos

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Nuria Montserrat

    (Center of Regenerative Medicine in Barcelona)

  • Ho-Lim Fung

    (University of California at San Diego)

  • Alessandra Giorgetti

    (Center of Regenerative Medicine in Barcelona)

  • Josipa Bilic

    (Center of Regenerative Medicine in Barcelona)

  • Erika M. Batchelder

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Holm Zaehres

    (Max Planck Institute for Molecular Biomedicine)

  • Hans R. Schöler

    (Max Planck Institute for Molecular Biomedicine)

  • Kun Zhang

    (University of California at San Diego)

  • Juan Carlos Izpisua Belmonte

    (Gene Expression Laboratory, Salk Institute for Biological Studies
    Center of Regenerative Medicine in Barcelona)

Abstract

Recent studies indicate that human-induced pluripotent stem cells contain genomic structural variations and point mutations in coding regions. However, these studies have focused on fibroblast-derived human induced pluripotent stem cells, and it is currently unknown whether the use of alternative somatic cell sources with varying reprogramming efficiencies would result in different levels of genetic alterations. Here we characterize the genomic integrity of eight human induced pluripotent stem cell lines derived from five different non-fibroblast somatic cell types. We show that protein-coding mutations are a general feature of the human induced pluripotent stem cell state and are independent of somatic cell source. Furthermore, we analyse a total of 17 point mutations found in human induced pluripotent stem cells and demonstrate that they do not generally facilitate the acquisition of pluripotency and thus are not likely to provide a selective advantage for reprogramming.

Suggested Citation

  • Sergio Ruiz & Athurva Gore & Zhe Li & Athanasia D. Panopoulos & Nuria Montserrat & Ho-Lim Fung & Alessandra Giorgetti & Josipa Bilic & Erika M. Batchelder & Holm Zaehres & Hans R. Schöler & Kun Zhang , 2013. "Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming," Nature Communications, Nature, vol. 4(1), pages 1-8, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2381
    DOI: 10.1038/ncomms2381
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