Author: ["Helena Kilpinen","Angela Goncalves","Andreas Leha","Vackar Afzal","Kaur Alasoo","Sofie Ashford","Sendu Bala","Dalila Bensaddek","Francesco Paolo Casale","Oliver J. Culley","Petr Danecek","Adam Faulconbridge","Peter W. Harrison","Annie Kathuria","Davis McCarthy","Shane A. McCarthy","Ruta Meleckyte","Yasin Memari","Nathalie Moens","Filipa Soares","Alice Mann","Ian Streeter","Chukwuma A. Agu","Alex Alderton","Rachel Nelson","Sarah Harper","Minal Patel","Alistair White","Sharad R. Patel","Laura Clarke","Reena Halai","Christopher M. Kirton","Anja Kolb-Kokocinski","Philip Beales","Ewan Birney","Davide Danovi","Angus I. Lamond","Willem H. Ouwehand","Ludovic Vallier","Fiona M. Watt","Richard Durbin","Oliver Stegle","Daniel J. Gaffney"]
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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. Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease. The Human Induced Pluripotent Stem Cells Initiative (HipSci) has resulted in the generation, genotyping and phenotyping of more than 700 human induced pluripotent stem (iPS) cell lines derived from 300 healthy individuals. Although analysis of these data indicates that most of the variations in phenotypes between cells arise from variations between individuals, the authors also assess the consequences of the rare genetic defects that are recurrently seen in iPS cells after reprogramming and provide a map of the common regulatory variants that can change the transcriptome of human pluripotent cells. This resource will be useful for genetic studies of complex traits and cancer.Cite this article
Kilpinen, H., Goncalves, A., Leha, A. et al. Common genetic variation drives molecular heterogeneity in human iPSCs. Nature 546, 370–375 (2017). https://doi.org/10.1038/nature22403 