Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.
Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.
Genome Biol. 2023 Sep 11;24(1):207. doi: 10.1186/s13059-023-03019-3.
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 to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees.
We find 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 embryoid bodies from a human-chimpanzee fused cell line, we also infer the proportion of inter-species regulatory differences due to changes in cis and trans elements between the species. Using the cis/trans inference and an analysis of transcription factor binding sites, we identify dozens of transcription factors whose inter-species differences in expression are affecting expression differences between humans and chimpanzees in hundreds of target genes.
Here, 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.
对猿类进行比较基因表达研究受到跨不同组织采样相关挑战的限制。在这里，我们使用类胚体的单细胞 RNA 测序，从三个人类和三个黑猩猩的 70 多种细胞类型中收集转录组数据。
我们发现了数百个在细胞类型中具有保守调控的基因，以及一些基因的调控可能在一个或少数几种细胞类型中受到定向选择的影响。使用人类-黑猩猩融合细胞系的类胚体，我们还推断了由于物种之间顺式和反式元件变化引起的种间调控差异的比例。使用顺式/反式推断和转录因子结合位点分析，我们鉴定了数十个转录因子，它们在物种间表达的差异影响了数百个靶基因中人类和黑猩猩之间的表达差异。
在这里，我们展示了迄今为止最全面的人类和黑猩猩比较基因表达数据集，包括与种间差异相关的调控机制目录。
