Spatial Atlas of Molecular Cell Types and AAV Accessibility across the Mouse Central Nervous System

Here, we employed in situ sequencing technique, STARmap PLUS, 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 230 molecularly defined cell types and 106 tissue regions with single-cell resolution. To create a transcriptome-wide spatial atlas, we further integrated the STARmap PLUS measurements with published scRNA-seq atlas, 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.eB, 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 provided a comprehensive, high resolution single-cell resource that integrates spatial molecular atlas, cell taxonomy, brain anatomy, and genetic manipulation accessibility of the mammalian central nervous system (CNS).

Citation: Shi, H., He, Y., Zhou, Y., Huang, J., Maher, K., Wang, B., Tang, Z., Luo, S., Tan, P., Wu, M. and Lin, Z., 2023. Spatial atlas of the mouse central nervous system at molecular resolution. Nature, pp.1-10.