A comprehensive cell-type taxonomy has been constructed for the entire macaque cortex using spatial transcriptomics (BGI’s Stereo-seq technology) and snRNA-seq technology. Through this work, researchers have revealed the relationship between cell-type composition and various primate brain regions. Deciphering the composition and spatial distribution patterns of cell subtypes in the cortex is crucial for understanding the organizational principles of primate brains. This work provides a guide for systematic analysis of cell-type distribution specificity and regional specificity within the cortex, as well as molecular features.
This work is published in Cell, in the paper, “Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.”
Understanding the composition and spatial distribution of cells in the brain, as well as the relationships between them, is a fundamental question in neuroscience. Compared to other species, primates have larger cortices and more cell types. For example, the macaque brain, with over six billion cells, can be classified into hundreds of cell types based on their molecular, morphological, or physiological features, and their spatial distribution spans hundreds of distinct brain regions.
In this study, scientists performed large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions with an independently developed method to prepare centimeter-scale thin slices of the macaque brain for the experiments. By combining large-scale single-cell transcriptome analysis, they obtained a comprehensive three-dimensional single-cell atlas of the entire cortex of the crab-eating macaque. In addition, the Stereo-seq data reveal the global distribution of 264 cell types and their marker genes. The data are now publicly available at https://macaque.digital-brain.cn/spatial-omics.
The findings suggest that glutamatergic neurons, GABAergic neurons, and non-neuronal cells exhibited distinct cortical and regional specificity in their distribution throughout the cerebral cortex. Interestingly, there was a significant correlation between the cell-type composition and the hierarchical organization of brain regions in the visual and somatosensory systems. Brain regions at the same hierarchical level tended to have similar cell-type compositions, revealing the relationship between cell composition and brain region structure.
Furthermore, through cross-species comparison with publicly available single-cell data from human and mouse brains, scientists identified glutamatergic neuron cells specific to primates, which are predominantly located in layer 4 and highly express genes associated with human diseases, including FOXP2, DCC, and EPHA3.
The team will continue to focus on the mechanisms and target development of brain diseases, brain cell and structural evolution, and cellular and molecular mechanisms of brain function.