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

Autor: John Alexander, Ivana Barbaric, Zoe Hewitt, Sian Gregory, Wolf Reik, Peter W. Andrews, Richard Weightman, Harry Moore, Simon Andrews, Oliver Thompson, Serena Nik-Zainal, Andrew Wood, Felix Krueger, Kosuke Yusa, Paul J. Gokhale, Ferdinand von Meyenn, Marta Milo
Přispěvatelé: von Meyenn, Ferdinand [0000-0001-9920-3075], Hewitt, Zoe [0000-0001-7519-7029], Alexander, John [0000-0003-3973-6501], Wood, Andrew [0000-0002-5973-2092], Weightman, Richard [0000-0002-2593-8631], Gregory, Sian [0000-0002-3014-2603], Krueger, Felix [0000-0002-5513-3324], Gokhale, Paul J. [0000-0001-7225-4403], Milo, Marta [0000-0002-6996-6431], Nik-Zainal, Serena [0000-0001-5054-1727], Yusa, Kosuke [0000-0002-3442-021X], Andrews, Peter W. [0000-0001-7215-4410], Apollo - University of Cambridge Repository, Gokhale, Paul J [0000-0001-7225-4403], Andrews, Peter W [0000-0001-7215-4410]
Rok vydání: 2020
Předmět:
0301 basic medicine
Mutation rate
49/47
DNA Mutational Analysis
631/532/2064/2117
Cell Culture Techniques
General Physics and Astronomy
medicine.disease_cause
38/70
Epigenesis
Genetic
0302 clinical medicine
Mutation Rate
38/23
Induced pluripotent stem cell
lcsh:Science
Mutation
Multidisciplinary
article
Chromatin
Cell biology
DNA methylation
DNA
Intergenic
Pluripotent Stem Cells
Embryonic stem cells
Science
631/114/2403
Biology
General Biochemistry
Genetics and Molecular Biology
Cell Line
631/208/726/649
03 medical and health sciences
13/100
medicine
Humans
Genetic variation
Epigenetics
Chromosomes
Human
X
Whole Genome Sequencing
Sequence Analysis
RNA
631/208/176/1988
General Chemistry
DNA Methylation
Embryonic stem cell
Culture Media
Oxygen
Oxidative Stress
030104 developmental biology
Cell culture
Gene ontology
lcsh:Q
030217 neurology & neurosurgery
Zdroj: Nature Communications, 11 (1)
Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020)
Nature Communications
ISSN: 2041-1723
Popis: 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.
Nature Communications, 11 (1)
ISSN:2041-1723
Databáze: OpenAIRE
Externí odkaz: