Embryoid bodies facilitate comparative analysis of gene expression in humans and chimpanzees across dozens of cell types

Abstract

Comparative gene expression studies in apes are fundamentally limited by the challenges associated with sampling across different tissues. Here, we used single-cell RNA-sequencing of embryoid bodies (EBs) to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees. We found hundreds of genes whose regulation is conserved across cell types, as well as genes whose regulation likely evolves under directional selection in one or a handful of cell types. Using EBs from a human-chimpanzee fused cell line, we also inferred the proportion of inter-species regulatory differences due to changes in cis and trans elements between the species. Thus, we present the most comprehensive dataset of comparative gene expression from humans and chimpanzees to date, including a catalog of regulatory mechanisms associated with inter-species differences.