TY - JOUR
T1 - Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
AU - HipSci Consortium
AU - Cuomo, Anna S.E.
AU - Seaton, Daniel D.
AU - McCarthy, Davis J.
AU - Martinez, Iker
AU - Bonder, Marc Jan
AU - Garcia-Bernardo, Jose
AU - Amatya, Shradha
AU - Madrigal, Pedro
AU - Isaacson, Abigail
AU - Buettner, Florian
AU - Knights, Andrew
AU - Natarajan, Kedar Nath
AU - Agu, Chukwuma A.
AU - Alderton, Alex
AU - Danecek, Petr
AU - Denton, Rachel
AU - Durbin, Richard
AU - Gaffney, Daniel J.
AU - Goncalves, Angela
AU - Halai, Reena
AU - Harper, Sarah
AU - Kirton, Christopher M.
AU - Kolb-Kokocinski, Anja
AU - Leha, Andreas
AU - McCarthy, Shane A.
AU - Memari, Yasin
AU - Patel, Minal
AU - Birney, Ewan
AU - Casale, Francesco Paolo
AU - Clarke, Laura
AU - Harrison, Peter W.
AU - Kilpinen, Helena
AU - Streeter, Ian
AU - Denovi, Davide
AU - Meleckyte, Ruta
AU - Moens, Natalie
AU - Watt, Fiona M.
AU - Ouwehand, Willem H.
AU - Lamond, Angus I.
AU - Bensaddek, Dalila
AU - Beales, Philip
AU - Vallier, Ludovic
AU - Marioni, John C.
AU - Chhatriwala, Mariya
AU - Stegle, Oliver
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079214042&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-14457-z
DO - 10.1038/s41467-020-14457-z
M3 - Article
C2 - 32041960
AN - SCOPUS:85079214042
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 810
ER -