Spatial and single-nucleus transcriptomic profile of a chimpanzee frontal pole

Abstract

Chimpanzees, our closest living relatives, share a vast amount of our genetic code, with the majority of differences found in non-coding regions of the genome. Functional and gene regulatory differences drive phenotypic divergence, including the distinctive brain anatomy of humans compared to chimpanzees and other apes. However, little is known about species differences in gene expression, and how they relate to the evolution of neuroanatomy and cognition. This is primarily due to the limited availability of great ape brain samples and challenges in comparative spatial transcriptomic studies. Here, we present the first spatial transcriptomic data from a chimpanzee brain based on post mortem tissue from an adult female, who was euthanised due to poor health. We focus on the frontal pole, a brain region that has undergone significant evolutionary changes in size and organisation since the last common ancestor of humans and chimpanzees, and is considered critical for cognitive evolution. We examined the gene expression profiles and cell-type composition of the frontal pole on the left hemisphere, including both neuronal and non-neuronal cell types across cortical layers and white matter. By integrating our spatial transcriptomic data with a publicly available single-nucleus transcriptomic dataset of the chimpanzee dorsolateral prefrontal cortex, we mapped the spatial distribution of 29 chimpanzee brain cell types. This study represents a first step towards characterisation of spatial gene regulatory differences between the brains of non-human great apes and humans. Significance statementRecent advances in spatial transcriptomics technologies provided important insights into the spatial organisation of gene expression and cell types in human and mouse brains, yet applications in non-model organisms remain limited. Here, we present the first-ever spatial transcriptomics dataset from a chimpanzee brain. We demonstrate i) the applicability of a widely used spatial transcriptomics technique to chimpanzee brain samples freshly frozen in isopentane, and ii) an end-to-end pipeline for generating good-quality spatial transcriptomics data from chimpanzee brains. Our work paves the way for future comparative spatial transcriptomics studies across human and non-human primate brains, and marks a step toward applying spatial omics methods to great ape brains.