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

Accepted version
Peer-reviewed

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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.

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Keywords

Cell Culture Techniques, Cell Line, Chromosomes, Human, X, Culture Media, DNA Methylation, DNA Mutational Analysis, DNA, Intergenic, Epigenesis, Genetic, Humans, Mutation Rate, Oxidative Stress, Oxygen, Pluripotent Stem Cells, Sequence Analysis, RNA, Whole Genome Sequencing

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research UK (23916)
Medical Research Council (MR/R015724/1)
Medical Research Council (MR/L012537/1)
Medical Research Council (MR/L012650/1)
Cancer Research UK (23433)