by Researchers at the Broad Institute of MIT and Harvard have developed a detailed atlas of cell types in the mammalian brain using a technology called spatial transcriptomics. This technology allows scientists to not only measure gene activity in individual cells, but also determine their location within tissues and organs. The atlas, described in the journal Nature, provides a comprehensive map of several thousand cell populations in the entire mouse brain, uncovering unexpected cellular diversity in understudied regions and providing new insights into brain structures.
Led by Evan Macosko and Fei Chen, the team analyzed the gene activity of individual cells throughout the mouse brain and assigned the cells’ locations within the tissue. They were able to identify an estimated 90% of all cell populations in the mouse brain, with the most diversity found in subcortical areas such as the midbrain, pons, medulla, and hypothalamus. These regions, which have received less research attention compared to the cortex, are believed to play a crucial role in brain function and possible disease mechanisms.
The researchers’ atlas represents the culmination of a decade of work, combining the development of spatial transcriptomics technology in their labs with the processing of the largest single-cell and spatial dataset ever generated. Their findings highlight the need for deeper study of understudied brain regions and provide valuable resources for the neuroscience community.
The study is part of a series of 10 papers in Nature that aim to map the mouse nervous system at the single-cell level. These studies, led by groups at the Broad Institute, Allen Institute for Brain Science, Salk Institute for Biological Studies, and other institutions supported by the National Institutes of Health’s BRAIN Initiative, collectively describe the first complete cell type atlas of a mammalian brain.
In a separate study published earlier, researchers led by Xiao Wang and Jia Liu used spatial transcriptomics technology to analyze the expression of over 1,000 genes in the mouse brain and spinal cord. Their research resulted in the identification of hundreds of cell types and provided highly precise tissue maps of the brain and spinal cord.
The team at the Broad Institute and the Macosko and Chen labs developed and applied their spatial transcriptomic approach to the entire mouse brain. By analyzing the full transcriptome of cells from multiple brain regions, they clustered the gene activity profiles into nearly 5,000 unique cell populations. They then used Slide-seq, a technique developed in their labs, to align the spatial data with a reference atlas, enabling the assignment of each transcript to a known brain structure.
The researchers hope that their atlas will empower and inspire further research within the scientific community. The spatial localizations and marker genes identified in the study can be used by other groups to study specific cell types or integrate with their own research. The atlas also sheds light on how neurotransmitters are used by different cell types in different brain regions and provides insights into the locations where disease-associated genes are active.
The comprehensive atlas of cell types in the mouse brain sets the stage for future efforts to map other organs in mice and eventually the human brain. The findings provide a crucial foundation for understanding the complexity of the brain and improving our knowledge of brain function and disease mechanisms.
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