Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach
To understand the mutational burden of human induced pluripotent stem cells (iPSCs), we sequenced genomes of 18 fibroblast-derived iPSC lines and identified different classes of somatic mutations based on structure, origin, and frequency. Copy-number alterations affected 295 kb in each sample and st...
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Published in | Cell reports (Cambridge) Vol. 24; no. 4; pp. 883 - 894 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
24.07.2018
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Subjects | |
Online Access | Get full text |
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Summary: | To understand the mutational burden of human induced pluripotent stem cells (iPSCs), we sequenced genomes of 18 fibroblast-derived iPSC lines and identified different classes of somatic mutations based on structure, origin, and frequency. Copy-number alterations affected 295 kb in each sample and strongly impacted gene expression. UV-damage mutations were present in ∼45% of the iPSCs and accounted for most of the observed heterogeneity in mutation rates across lines. Subclonal mutations (not present in all iPSCs within a line) composed 10% of point mutations and, compared with clonal variants, showed an enrichment in active promoters and increased association with altered gene expression. Our study shows that, by combining WGS, transcriptome, and epigenome data, we can understand the mutational burden of each iPSC line on an individual basis and suggests that this information could be used to prioritize iPSC lines for models of specific human diseases and/or transplantation therapy.
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•Mutations due to UV-damage are present in ∼50% of iPSCs derived from skin fibroblasts•Clonal and subclonal UV-damage mutations are associated with different chromatin states•Subclonal mutations are enriched in active promotors and tend to alter gene expression•Subclonal mutations tend not to evolve during passaging and differentiation
To understand the mutational burden of iPSCs, D’Antonio et al. sequenced genomes from 18 lines and identified four somatic mutation classes: clonal, subclonal, UV-damage mutations, and CNAs. Annotating mutations based on their class and the chromatin state in which they occur enables prediction of their influence on gene expression. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2018.06.091 |