The molecular cytoarchitecture of the adult mouse brain

Jonah Langlieb, Nina S. Sachdev, Karol S. Balderrama, Naeem M. Nadaf, Mukund Raj, Evan Murray, James T. Webber, Charles Vanderburg, Vahid Gazestani, Daniel Tward, Chris Mezias, Xu Li, Katelyn Flowers, Dylan M. Cable, Tabitha Norton, Partha Mitra, Fei Chen () and Evan Z. Macosko ()
Additional contact information
Jonah Langlieb: Broad Institute of Harvard and MIT
Nina S. Sachdev: Broad Institute of Harvard and MIT
Karol S. Balderrama: Broad Institute of Harvard and MIT
Naeem M. Nadaf: Broad Institute of Harvard and MIT
Mukund Raj: Broad Institute of Harvard and MIT
Evan Murray: Broad Institute of Harvard and MIT
James T. Webber: Broad Institute of Harvard and MIT
Charles Vanderburg: Broad Institute of Harvard and MIT
Vahid Gazestani: Broad Institute of Harvard and MIT
Daniel Tward: University of California, Los Angeles
Chris Mezias: Cold Spring Harbor Laboratory
Xu Li: Cold Spring Harbor Laboratory
Katelyn Flowers: Broad Institute of Harvard and MIT
Dylan M. Cable: Broad Institute of Harvard and MIT
Tabitha Norton: Broad Institute of Harvard and MIT
Partha Mitra: Cold Spring Harbor Laboratory
Fei Chen: Broad Institute of Harvard and MIT
Evan Z. Macosko: Broad Institute of Harvard and MIT

Nature, 2023, vol. 624, issue 7991, 333-342

Abstract: Abstract The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2—a recently developed spatial transcriptomics method with near-cellular resolution—across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource ( www.BrainCellData.org ), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.

Date: 2023
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DOI: 10.1038/s41586-023-06818-7

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