Genome damage in induced pluripotent stem cells: Assessing the mechanisms and their consequences

Authors

  • Samer M. I. Hussein,

    1. Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada
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    • Both the authors contributed equally to this work.

  • Judith Elbaz,

    1. Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada
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    • Both the authors contributed equally to this work.

  • Andras A. Nagy

    Corresponding author
    1. Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada
    2. Department of Obstetrics and Gynaecology and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    • Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.
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Abstract

In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally differentiated somatic cells to a pluripotent stem cell state. The resulting induced pluripotent stem cells (iPSCs) made a paradigm shift in the field, further nailing down the disproval of the long-held dogma that differentiation is unidirectional. The prospect of using iPSCs for patient-specific cell-based therapies has been enticing. This promise, however, has been questioned in the last two years as several studies demonstrated intrinsic epigenetic and genomic anomalies in these cells. Here, we not only review the recent critical studies addressing the genome integrity during the reprogramming process, but speculate about the underlying mechanisms that could create de novo genome damage in iPSCs. Finally, we discuss how much an elevated mutation load really matters considering the safety of future therapies with cells heavily cultured in vitro.

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