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Chunk #1 — Introduction

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Common genetic variation drives molecular heterogeneity in human iPSCs.
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The Human Induced Pluripotent Stem Cells Initiative (HipSci: www.hipsci.org) was established to generate a large, high-quality, open-access reference panel of human iPSC lines. A major focus of the initiative is the systematic derivation of iPSCs from hundreds of healthy volunteers using a standardised and well-defined experimental pipeline. The lines are extensively characterised and available to the wider research community along with the accompanying genetic and phenotypic data. Here, we report initial results from the characterization of the first 711 iPSC lines derived from 301 healthy individuals. We provide a high-resolution map of recurrent copy number aberrations in iPSCs, identify putative candidate genes under selection in these regions, and assess the functional consequences of these changes. We show that common genetic variants produce readily detectable effects in iPSCs and provide the most comprehensive map of regulatory variation in human iPSCs to date. We also demonstrate that differences between donor individuals have pervasive effects at all phenotypic levels in iPSCs, from the epigenome, transcriptome and proteome to cell differentiation and morphology.