5 years ago

Common genetic variation drives molecular heterogeneity in human iPSCs

Common genetic variation drives molecular heterogeneity in human iPSCs
Oliver Stegle, Daniel J. Gaffney, Annie Kathuria, Sharad R. Patel, Vackar Afzal, Ludovic Vallier, Sofie Ashford, Rachel Nelson, Alex Alderton, Helena Kilpinen, Davide Danovi, Sendu Bala, Sarah Harper, Alice Mann, Richard Durbin, Willem H. Ouwehand, Filipa Soares, Anja Kolb-Kokocinski, Ruta Meleckyte, Angela Goncalves, Angus I. Lamond, Davis McCarthy, Andreas Leha, Reena Halai, Peter W. Harrison, Petr Danecek, Francesco Paolo Casale, Oliver J. Culley, Kaur Alasoo, Adam Faulconbridge, Minal Patel, Laura Clarke, Alistair White, Yasin Memari, Philip Beales, Shane A. McCarthy, Christopher M. Kirton, Ewan Birney, Dalila Bensaddek, Nathalie Moens, Fiona M. Watt, Chukwuma A. Agu, Ian Streeter
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.

Publisher URL: http://dx.doi.org/10.1038/nature22403

DOI: 10.1038/nature22403

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