Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
复制标题
DOI：
10.1038/s41467-020-14457-z
复制
发表时间：
2020-02-10
影响因子：
16.6
通讯作者：
Stegle, Oliver
中科院分区：
文献类型：
--
作者：
Cuomo, Anna S. E.;Seaton, Daniel D.;Stegle, Oliver
干细胞生物学的最新发展使研究早期人类发育过程中细胞命运的决定成为可能，而这在体内是不可能研究的。然而，了解个体之间的发育差异，特别是在这一过程中常见遗传变异的影响尚未得到描述。在这里，我们利用来自125个供体的人类iPS细胞系，采用合并实验设计和单细胞rna测序来研究内胚层分化的群体变异。我们确定了预测单个品系分化效率的分子标记，并利用个体遗传背景的异质性来绘制数百个表达数量性状位点，这些位点在分化过程中和细胞环境中动态影响表达。
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.