Common genetic variation drives molecular heterogeneity in human iPSCs

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 SoaresAlice 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

346 Citations (Scopus)
129 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)370-375
Number of pages6
JournalNATURE
Volume546
Issue number7658
Early online date10 May 2017
DOIs
Publication statusPublished - 15 Jun 2017

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