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Nat Commun. 2020 Feb 10;11(1):810. doi: 10.1038/s41467-020-14457-z.

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

Author information

1
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton, Cambridge, UK.
2
St Vincent's Institute of Medical Research, Fitzroy, Victoria, 3065, Australia.
3
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
4
Wellcome Trust-MRC Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, CB2 0SZ, UK.
5
Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
6
GeneLab, AWG Multi-Omics/System Biology, NASA Ames Research Center, Moffett Field, California, USA.
7
Danish Institute of Advanced Study (D-IAS), Functional Genomics and Metabolism Unit, University of Southern Denmark, Odense, Denmark.
8
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK. lv225@cam.ac.uk.
9
Wellcome Trust-MRC Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, CB2 0SZ, UK. lv225@cam.ac.uk.
10
Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK. lv225@cam.ac.uk.
11
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton, Cambridge, UK. marioni@ebi.ac.uk.
12
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK. marioni@ebi.ac.uk.
13
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. marioni@ebi.ac.uk.
14
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK. mc18@sanger.ac.uk.
15
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton, Cambridge, UK. o.stegle@dkfz.de.
16
Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. o.stegle@dkfz.de.
17
European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany. o.stegle@dkfz.de.

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.

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