An analysis that identifies 75 distinct cell types present in a region of the human cerebral cortex is presented in Nature this week. By comparing these data to those from an analogous region of the mouse brain, the study reveals similarities in their architecture and cell types - but also extensive differences. The findings emphasize the importance of studying the human brain directly, in addition to the use of model organisms.

Compared to the cerebral cortex of the mouse, the human cortex is over 1,000 times larger by area and the number of neurons. Although the basic architecture appears to be conserved in mammalian species, previous research has suggested that there are differences in the cellular makeup of the human cortex.

Ed Lein and colleagues used single-nucleus RNA sequencing to classify the cell types in the middle temporal gyrus (a region within the cortex) of the human brain. Their analysis revealed 75 distinct cell types, including 6 non-neuronal, 24 excitatory and 45 inhibitory cells. Using mouse single-cell RNA-sequencing datasets, they then compared the human and mouse cortex and found that most of the cell types identified in humans had corresponding cell types in mice.

However, the authors also found that there were differences in the levels of gene expression between the corresponding cell types. For example, serotonin receptors were the second most divergent gene family between the two species. The authors suggest that this may challenge the use of mouse models for neuropsychiatric disorders that involve serotonin signalling.