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

Cuomo, ASE; Seaton, DD; McCarthy, DJ; Martinez, I; Bonder, MJ; Garcia-Bernardo, J; Amatya, S; ... Stegle, O; + view all (2020) Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression. Nature Communications , 11 (1) p. 810. 10.1038/s41467-020-14457-z. Green open access

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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.

Type: Article
Title: Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-020-14457-z
Publisher version: http://dx.doi.org/10.1038/s41467-020-14457-z
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10092738
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