Dataset Information

Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach.

ABSTRACT: 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.

SUBMITTER: D'Antonio M

PROVIDER: S-EPMC6467479 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach.

D'Antonio Matteo M Benaglio Paola P Jakubosky David D Greenwald William W WW Matsui Hiroko H Donovan Margaret K R MKR Li He H Smith Erin N EN D'Antonio-Chronowska Agnieszka A Frazer Kelly A KA

Cell reports 20180701 4

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 pre ...[more]

PMID: 30044985

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Dataset Information

Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach.

Publications

Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach.

Similar Datasets

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