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

被引：59

作者：

D'Antonio, Matteo ^{[1
]}

Benaglio, Paola ^{[1
]}

Jakubosky, David ^{[2
,3
]}

Greenwald, William W. ^{[4
]}

Matsui, Hiroko ^{[1
]}

Donovan, Margaret K. R. ^{[3
,4
]}

Li, He ^{[1
]}

Smith, Erin N. ^{[5
,6
]}

D'Antonio-Chronowska, Agnieszka ^{[1
]}

Frazer, Kelly A. ^{[1
,5
,6
]}

机构：

[1] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Dept Biomed Informat, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Bioinformat & Syst Biol, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Rady Childrens Hosp, La Jolla, CA 92093 USA

来源：

CELL REPORTS | 2018年 / 24卷 / 04期

关键词：

GENETIC-VARIATION; SOMATIC MUTATIONS; POINT MUTATIONS; COPY NUMBER; CANCER; GENOME; EXPRESSION; SIGNATURES; HETEROGENEITY; ALIGNMENT;

D O I：

10.1016/j.celrep.2018.06.091

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：883 / 894

页数：12

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