Spatial atlas of the mouse central nervous system at molecular resolution

Hailing Shi, Yichun He, Yiming Zhou, Jiahao Huang, Kamal Maher, Brandon Wang, Zefang Tang, Shuchen Luo, Peng Tan, Morgan Wu, Zuwan Lin, Jingyi Ren, Yaman Thapa, Xin Tang, Ken Y. Chan, Benjamin E. Deverman, Hao Shen, Albert Liu, Jia Liu () and Xiao Wang ()
Additional contact information
Hailing Shi: Broad Institute of MIT and Harvard
Yichun He: Broad Institute of MIT and Harvard
Yiming Zhou: Broad Institute of MIT and Harvard
Jiahao Huang: Broad Institute of MIT and Harvard
Kamal Maher: Broad Institute of MIT and Harvard
Brandon Wang: Broad Institute of MIT and Harvard
Zefang Tang: Broad Institute of MIT and Harvard
Shuchen Luo: Broad Institute of MIT and Harvard
Peng Tan: Broad Institute of MIT and Harvard
Morgan Wu: Broad Institute of MIT and Harvard
Zuwan Lin: Broad Institute of MIT and Harvard
Jingyi Ren: Broad Institute of MIT and Harvard
Yaman Thapa: Broad Institute of MIT and Harvard
Xin Tang: Broad Institute of MIT and Harvard
Ken Y. Chan: Broad Institute of MIT and Harvard
Benjamin E. Deverman: Broad Institute of MIT and Harvard
Hao Shen: Harvard University
Albert Liu: Broad Institute of MIT and Harvard
Jia Liu: Harvard University
Xiao Wang: Broad Institute of MIT and Harvard

Nature, 2023, vol. 622, issue 7983, 552-561

Abstract: Abstract Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain1,2, but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS3,4, to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm3, mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas1, imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB5,6. Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system.

Date: 2023
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DOI: 10.1038/s41586-023-06569-5

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