Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.
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Authors
Rouhani, Foad J
Wuster, Arthur
Li, Yilong
Conte, Nathalie
Koike-Yusa, Hiroko
Kumasaka, Natsuhiko
Yusa, Kosuke
Publication Date
2016-04Journal Title
PLoS Genet
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Volume
12
Issue
4
Pages
e1005932
Language
eng
Type
Article
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Rouhani, F. J., Nik-Zainal, S., Wuster, A., Li, Y., Conte, N., Koike-Yusa, H., Kumasaka, N., et al. (2016). Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.. PLoS Genet, 12 (4), e1005932. https://doi.org/10.1371/journal.pgen.1005932
Abstract
The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer.
Keywords
Cells, Cultured, Humans, Cell Lineage, Mutation, Polymorphism, Single Nucleotide, Adult, Middle Aged, Male, Young Adult, Induced Pluripotent Stem Cells
Sponsorship
Medical Research Council (MC_PC_12009)
Identifiers
External DOI: https://doi.org/10.1371/journal.pgen.1005932
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280540
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