TY - JOUR
KW - Cells, Cultured
KW - Cellular Reprogramming
KW - DNA Copy Number Variations
KW - Gene Expression Regulation
KW - Genetic Variation
KW - Genotype
KW - Humans
KW - induced pluripotent stem cells
KW - Organ Specificity
KW - Phenotype
KW - Quality Control
KW - Quantitative Trait Loci
KW - Transcriptome
AU - Helena Kilpinen
AU - Angela Goncalves
AU - Andreas Leha
AU - Vackar Afzal
AU - Kaur Alasoo
AU - Sofie Ashford
AU - Sendu Bala
AU - Dalila Bensaddek
AU - Francesco Paolo Casale
AU - Oliver J. Culley
AU - Petr Danecek
AU - Adam Faulconbridge
AU - Peter W. Harrison
AU - Annie Kathuria
AU - Davis McCarthy
AU - Shane A. McCarthy
AU - Ruta Meleckyte
AU - Yasin Memari
AU - Nathalie Moens
AU - Filipa Soares
AU - Alice Mann
AU - Ian Streeter
AU - Chukwuma A. Agu
AU - Alex Alderton
AU - Rachel Nelson
AU - Sarah Harper
AU - Minal Patel
AU - Alistair White
AU - Sharad R. Patel
AU - Laura Clarke
AU - Reena Halai
AU - Christopher M. Kirton
AU - Anja Kolb-Kokocinski
AU - Philip Beales
AU - Ewan Birney
AU - Davide Danovi
AU - Angus I. Lamond
AU - Willem H. Ouwehand
AU - Ludovic Vallier
AU - Fiona M. Watt
AU - Richard Durbin
AU - Oliver Stegle
AU - Daniel J. Gaffney
AB - 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.
BT - Nature
DA - 2017-06-15
DO - 10.1038/nature22403
IS - 7658
LA - eng
N2 - 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.
PY - 2017
SP - 370
EP - 375
T2 - Nature
TI - Common genetic variation drives molecular heterogeneity in human iPSCs
VL - 546
SN - 1476-4687
ER -