Scientists map single-cell spatial distribution

About 100 scientists recently mapped cell-type taxonomy in the macaque cortex and revealed relationships between cell-type composition and different primate brain regions using self-developed spatial transcriptome sequencing technology stereo-seq and snRNA-seq technology. This provides a molecular and cellular basis for further investigation of neural circuits.

The study was published in CellScientists from the Chinese Academy of Sciences’ Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, BGI Research, Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Technology, and Tencent AI Lab. Karolinska Institutet and KTH Royal Institute of Technology in Sweden,

Primates have large numbers of neurons that form complex and intricate neural circuits that support advanced cognition and behavior. Malfunctions in these cells and circuits can lead to various brain disorders. Understanding the structure and spatial distribution of brain cells and their relationships is a fundamental question in neuroscience, comparable to the periodic table in chemistry, the world map in geological discoveries, or the basic sequence of DNA discovered through humans. Genome sequencing.

Compared to other species, primates, including macaques, the closest animal model to humans, have higher cognitive and social abilities, as well as larger cortices and more cell types. For example, the macaque brain, which contains more than six billion cells, can be classified into hundreds of cell types based on their molecular, morphological, or physiological characteristics, and their spatial distribution spans hundreds of different brain regions. Understanding the composition and spatial distribution patterns of cell subtypes in the cortex is critical to understanding the organization principles of the primate brain.

In this study, the scientists used a newly developed large-field-of-view spatial transcriptome method, called Stereo-Seq, and an independently developed method to prepare centimeter-scale thin slices of macaque brains for experiments. Combining large-scale single-cell transcriptome analysis, they obtained a comprehensive three-dimensional single-cell atlas of the entire cortex of crab-eating macaques, providing guidance for systematic analysis of cell-type distribution specificity and regional specificity. cortex, as well as molecular features.

In addition, the scientists found that glutamatergic neurons, GABAergic neurons, and non-neuronal cells exhibit distinct cortical and regional specificities in their distribution throughout the cerebral cortex. Interestingly, there was a significant correlation between cell-type composition and hierarchical organization of brain regions in the visual and somatosensory systems. Brain regions at the same hierarchical level tend to have similar cell-type compositions, revealing a relationship between cell composition and brain region composition.

Additionally, through cross-species comparisons with publicly available single-cell data from human and mouse brains, the scientists identified glutamatergic neuron cells specific to primates, located predominantly in layer 4, and genes highly associated with human disease. FOXP2, DCCAnd EPHA3.

This study generated a comprehensive dataset of single-cell and spatial transcriptomics for the entire macaque cerebral cortex, providing an important data resource for future research. The data are now publicly available at https://macaque.digital-brain.cn/spatial-omics.

In the future, the team will continue to focus on the mechanisms of brain diseases and target development, structural evolution of brain cells, and cellular and molecular mechanisms of brain function.

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