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 J. 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 L. Beales, Ewan Birney, Davide Danovi, Angus I. Lamond, Willem H. Ouwehand, Ludovic Vallier, Fiona M. Watt (Lead / Corresponding author), Richard Durbin (Lead / Corresponding author), Oliver Stegle (Lead / Corresponding author), Daniel J. Gaffney (Lead / Corresponding author)

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    Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: Our study outlines the major sources of genetic and phenotypic variation in iPSCs 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 iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and 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
    Issue number7658
    Early online date10 May 2017
    Publication statusPublished - 15 Jun 2017


    • Induced pluripotent stem cells
    • Gene expression
    • Gene regulation
    • Genetic variation


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    • Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs (Nature (2017) 546 (370-375) DOI: 10.1038/nature22403)

      Kilpinen, H., Goncalves, A., Leha, A., Afzal, V., Alasoo, K., Ashford, S., Bala, S., Bensaddek, D., Casale, F. P., Culley, O. J., Danecek, P., Faulconbridge, A., Harrison, P. W., Kathuria, A., McCarthy, D. J., McCarthy, S. A., Meleckyte, R., Memari, Y., Moens, N., Soares, F., & 23 othersMann, A., Streeter, I., Agu, C. A., Alderton, A., Nelson, R., Harper, S., Patel, M., White, A., Patel, S. R., Clarke, L., Halai, R., Kirton, C. M., Kolb-Kokocinski, A., Beales, P. L., Birney, E., Danovi, D., Lamond, A., Ouwehand, W. H., Vallier, L., Watt, F. M., Durbin, R., Stegle, O. & Gaffney, D. J., 29 Jun 2017, In: Nature. 546, 7660, p. 686 1 p.

      Research output: Contribution to journalComment/debatepeer-review

      Open Access
      12 Citations (Scopus)

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