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Nature. 2017 Jun 15;546(7658):370-375. doi: 10.1038/nature22403. Epub 2017 May 10.

Common genetic variation drives molecular heterogeneity in human iPSCs.

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European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Centre for Gene Regulation &Expression, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Centre for Stem Cells &Regenerative Medicine, King's College London, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
Wellcome Trust and MRC Cambridge Stem Cell Institute and Biomedical Research Centre, Anne McLaren Laboratory, Department of Surgery, University of Cambridge, Cambridge CB2 0SZ, UK.
UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.


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.

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