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Nature ; 546(7658): 370-375, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28489815

RESUMO

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.


Assuntos
Variação Genética/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Cultivadas , Reprogramação Celular/genética , Variações do Número de Cópias de DNA/genética , Regulação da Expressão Gênica/genética , Genótipo , Humanos , Especificidade de Órgãos , Fenótipo , Controle de Qualidade , Locos de Características Quantitativas/genética , Transcriptoma/genética
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