Single-Cell Sequencing Reveals Lineage-Specific Dynamic Genetic Regulation of Gene Expression During Human Cardiomyocyte Differentiation

• DOI: 10.1101/2021.06.03.446970
• Publication Date: 2021-06-04T00:00:55Z
• Authors: Reem Elorbany; Joshua M Popp; Katherine Rhodes; Benjamin J Strober; Kenneth Barr; Guanghao Qi; Yoav Gilad; Alexis Battle
• Keywords: Cell type; Lineage (genetic); Single-Cell Analysis; Gene regulatory network

Abstract Dynamic and temporally specific gene regulatory changes may underlie unexplained genetic associations with complex disease. During a dynamic process such as cellular differentiation, the overall cell type composition of tissue (or an in vitro culture) profile each can both experience significant over time. To identify these effects high resolution, we collected single-cell RNA-sequencing data differentiation time course from induced pluripotent stem cells to cardiomyocytes, sampled at 7 unique points 19 human lines. We employed flexible approach map eQTLs whose vary significantly bifurcating trajectories, including many are one two lineages. Our study design allowed us distinguish true affecting lineage expression driven by potentially non-genetic differences between lines composition. Additionally, used profiles learned deconvolve re-analyze matched bulk RNA-seq samples. Using this approach, were able large number novel single while also attributing particular lineage. Overall, found that using uncover provide new insight into occur among heterogeneous types during cardiomyocyte differentiation.