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

Anna S. E. Cuomo; Daniel D. Seaton; Davis James McCarthy; Iker Martinez; Marc Jan Bonder; José Garcia‐Bernardo; Shradha Amatya; Pedro Madrigal; Abigail Isaacson; Florian Buettner; Andrew J. Knights; Kedar Nath Natarajan; Chukwuma A. Agu; Alex Alderton; Petr Danecek; Rachel Denton; Richard Michael Durbin; Daniel J. Gaffney; Ângela Gonçalves; Reena Halai; Sarah Harper; Christopher M. Kirton; Anja Kolb‐Kokocinski; Andreas Leha; Shane McCarthy; Yasin Memari; Minal J Patel; Ewan Birney; Francesco Paolo Casale; Laura Clarke

doi:10.1038/s41467-020-14457-z

GenomicsNature CommunicationsFeb 10, 2020

Peer-reviewed journal article

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

Anna S. E. Cuomo iD, Daniel D. Seaton iD, Davis James McCarthy iD, Iker Martinez, Marc Jan Bonder iD, José Garcia‐Bernardo iD, Shradha Amatya, Pedro Madrigal iD, Abigail Isaacson iD, Florian Buettner iD, Andrew J. Knights iD, Kedar Nath Natarajan iD, Chukwuma A. Agu iD, Alex Alderton, Petr Danecek iD, Rachel Denton, Richard Michael Durbin iD, Daniel J. Gaffney iD, Ângela Gonçalves iD, Reena Halai, Sarah Harper, Christopher M. Kirton, Anja Kolb‐Kokocinski, Andreas Leha iD, Shane McCarthy iD, , Oliver Stegle iD

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, 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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