Spatial Atlas of the Mouse Central Nervous System at Molecular Resolution
Spatial Atlas of the Mouse Central Nervous System at Molecular Resolution
Abstract Spatially charting molecular cell types at single-cell resolution across the three-dimensional (3D) volume of the brain is critical for illustrating the molecular basis of the brain anatomy and functions. Single-cell RNA sequencing (scRNA-seq) has profiled molecular cell types in the mouse brain1, 2, but cannot capture their spatial organization. Here, we employed an in situ sequencing technique, STARmap PLUS3, 4, to map more than one million high-quality cells across the whole adult mouse brain and the spinal cord, profiling 1,022 genes at subcellular resolution with a voxel size of 194 X 194 X 345 nm in 3D. We developed computational pipelines to segment, cluster, and annotate 231 molecularly defined cell types and 64 tissue regions with single-cell resolution. To create a transcriptome-wide spatial atlas, we further integrated the STARmap PLUS measurements with a published scRNA-seq atlas1, imputing 11,844 genes at the single-cell level. Finally, we engineered a highly expressed RNA barcoding system to delineate the tropism of a brain-wide transgene delivery tool, AAV-PHP.eB5, 6, revealing its single-cell resolved transduction efficiency across the molecular cell types and tissue regions of the whole mouse brain. Together, our datasets and annotations provide a comprehensive, high-resolution single-cell resource that integrates a spatial molecular atlas, cell taxonomy, brain anatomy, and genetic manipulation accessibility of the mammalian central nervous system (CNS).
Ren Jingyi、Huang Jiahao、Wang Brandon、Tang Zefang、Tan Peng、Wu Morgan、Lin Zuwan、Tang Xin、Liu Albert、Liu Jia、Shi Hailing、Zhou Yiming、Thapa Yaman、Wang Xiao、He Yichun
Broad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||Klarman Cell Observatory, Broad Institute of MIT and HarvardBroad Institute of MIT and HarvardBroad Institute of MIT and Harvard||Department of Chemistry and Chemical Biology, Harvard UniversityBroad Institute of MIT and Harvard||John A. Paulson School of Engineering and Applied Sciences, Harvard UniversityBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyJohn A. Paulson School of Engineering and Applied Sciences, Harvard UniversityBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||School of Natural Science, Caldwell UniversityBroad Institute of MIT and Harvard||Department of Chemistry, Massachusetts Institute of TechnologyBroad Institute of MIT and Harvard||John A. Paulson School of Engineering and Applied Sciences, Harvard University
分子生物学细胞生物学神经病学、精神病学
Ren Jingyi,Huang Jiahao,Wang Brandon,Tang Zefang,Tan Peng,Wu Morgan,Lin Zuwan,Tang Xin,Liu Albert,Liu Jia,Shi Hailing,Zhou Yiming,Thapa Yaman,Wang Xiao,He Yichun.Spatial Atlas of the Mouse Central Nervous System at Molecular Resolution[EB/OL].(2025-03-28)[2025-08-03].https://www.biorxiv.org/content/10.1101/2022.06.20.496914.点此复制
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