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Common genetic variation drives molecular heterogeneity in human iPSCs.

Accepted version
Peer-reviewed

Type

Article

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Authors

Kilpinen, Helena 
Goncalves, Angela 
Leha, Andreas 
Afzal, Vackar 
Alasoo, Kaur 

Abstract

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Description

Keywords

Cells, Cultured, Cellular Reprogramming, DNA Copy Number Variations, Gene Expression Regulation, Genetic Variation, Genotype, Humans, Induced Pluripotent Stem Cells, Organ Specificity, Phenotype, Quality Control, Quantitative Trait Loci, Transcriptome

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

546

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_PC_12009)
Engineering and Physical Sciences Research Council (TS/H001220/1)
Medical Research Council (MC_PC_12026)
Medical Research Council (MR/L016311/1)
Wellcome Trust (098503/B/12/Z)
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