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Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions

Author

Listed:
  • Oliver Thompson

    (University of Sheffield, Western Bank)

  • Ferdinand Meyenn

    (Epigenetics Programme, Babraham Institute
    King’s College London
    Nutrition and Health, ETH Zurich)

  • Zoe Hewitt

    (University of Sheffield, Western Bank)

  • John Alexander

    (University of Sheffield, Western Bank
    The Institute of Cancer Research)

  • Andrew Wood

    (University of Sheffield, Western Bank)

  • Richard Weightman

    (University of Sheffield, Western Bank)

  • Sian Gregory

    (University of Sheffield, Western Bank)

  • Felix Krueger

    (Bioinformatics Group, Babraham Institute)

  • Simon Andrews

    (Bioinformatics Group, Babraham Institute)

  • Ivana Barbaric

    (University of Sheffield, Western Bank)

  • Paul J. Gokhale

    (University of Sheffield, Western Bank)

  • Harry D. Moore

    (University of Sheffield, Western Bank)

  • Wolf Reik

    (Epigenetics Programme, Babraham Institute
    Wellcome Genome Campus, Hinxton)

  • Marta Milo

    (University of Sheffield, Western Bank)

  • Serena Nik-Zainal

    (Wellcome Genome Campus, Hinxton
    Cambridge Biomedical Research Campus
    University of Cambridge, Hutchinson/MRC Research Centre, Box 1297, Cambridge Biomedical Campus)

  • Kosuke Yusa

    (Wellcome Genome Campus, Hinxton
    Kyoto University)

  • Peter W. Andrews

    (University of Sheffield, Western Bank)

Abstract

The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is of concern for their clinical application. However, the effect of different culture conditions on the underlying mutation rate is unknown. Here we show that the mutation rate in two human embryonic stem cell lines derived and banked for clinical application is low and not substantially affected by culture with Rho Kinase inhibitor, commonly used in their routine maintenance. However, the mutation rate is reduced by >50% in cells cultured under 5% oxygen, when we also found alterations in imprint methylation and reversible DNA hypomethylation. Mutations are evenly distributed across the chromosomes, except for a slight increase on the X-chromosome, and an elevation in intergenic regions suggesting that chromatin structure may affect mutation rate. Overall the results suggest that pluripotent stem cells are not subject to unusually high rates of genetic or epigenetic alterations.

Suggested Citation

  • Oliver Thompson & Ferdinand Meyenn & Zoe Hewitt & John Alexander & Andrew Wood & Richard Weightman & Sian Gregory & Felix Krueger & Simon Andrews & Ivana Barbaric & Paul J. Gokhale & Harry D. Moore & , 2020. "Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15271-3
    DOI: 10.1038/s41467-020-15271-3
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