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Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Cuomo, Anna SE 
Martinez, Iker 
Bonder, Marc Jan 

Abstract

Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency of individual lines, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts.

Description

Keywords

Cell Differentiation, Cell Line, Endoderm, Female, Gene Expression, Gene Expression Profiling, Gene-Environment Interaction, Genetic Association Studies, Genetic Heterogeneity, Humans, Induced Pluripotent Stem Cells, Male, Quantitative Trait Loci, Single-Cell Analysis

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (098503/B/12/Z)
Engineering and Physical Sciences Research Council (TS/H001220/1)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/M008975/1)
European Research Council (741707)
Medical Research Council (MC_PC_17230)
Cancer Research UK (22231)
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