Transcriptome map of the human brain at the single-cell resolution

The human brain is about three times larger than the brain of our closest relatives, chimpanzees and bonobos. However, increased size alone fails to explain cognitive abilities unique to humans. Functional changes acquired in the human lineage are likely mediated by divergent gene expression and cell composition in brain regions. Here we generated a map of the human brain transcriptome by assessing the gene expression levels in 33 distinct regions representing all major brain structures from four adult cognitively healthy human individuals, three chimpanzees, three bonobos, and three rhesus macaques. We further conducted single-nuclei RNA-sequencing (SN-seq) experiment in three of the 33 brain regions in four species: two regions showing excess of the human-specific differences, cingulate anterior cortex and cerebellar gray matter, as well as one region showing no such excess, caudate nucleus. We determined cell type specificity of human-specific differences observed in the bulk tissue analysis, and identified species-specific expression differences directly using SN-seq data. This data resource forms a comprehensive baseline for studies of normal and abnormal human brain function and evolution. 422 polyA-selected RNA-seq samples were obtained from 33 brain regions representing all major brain structures from four adult cognitively healthy human individuals, three chimpanzees, three bonobos, and three rhesus macaques