Journal
CELL REPORTS
Volume 24, Issue 4, Pages 883-894Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.06.091
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Funding
- California Institute for Regenerative Medicine (CIRM) [GC1R-06673]
- NIH [HG008118-01, HL107442-05, DK105541-03, DK112155-01, P30CA023100]
- National Library of Medicine Training [T15LM011271]
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To understand the mutational burden of human induced pluripotent stemcells (iPSCs), wesequenced genomes of 18 fibroblast-derived iPSClines and identified different classes of somaticmutations 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 similar to 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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