诱导多能干细胞分化过程中的单细胞 RNA 测序揭示了基因表达的动态遗传效应。

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

机构信息

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton, Cambridge, UK.

St Vincent's Institute of Medical Research, Fitzroy, Victoria, 3065, Australia.

出版信息

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

DOI:10.1038/s41467-020-14457-z

PMID:32041960

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7010688/

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.

摘要

近年来，干细胞生物学的发展使得人们能够研究早期人类发育过程中的细胞命运决定，而这些在体内是不可能研究的。然而，人们还没有了解到个体之间的发育是如何变化的，特别是在这个过程中常见遗传变异的影响。在这里，我们利用来自 125 个供体的人类诱导多能干细胞系、一个汇集的实验设计和单细胞 RNA 测序来研究内胚层分化的群体变异。我们确定了可预测个体系分化效率的分子标记，并利用个体间遗传背景的异质性来绘制数百个影响分化过程中动态表达的数量性状基因座，以及跨细胞环境的表达。