Spatial atlas of the mouse central nervous system at molecular resolution

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.

AI-assisted mass spectrometry imaging with in situ image segmentation for subcellular metabolomics analysis

“…8,9 The combination of AI and MSI technology has greatly promoted spatial metabolomics analysis for abundant scientific research. 2,10…”

Single-cell and spatial multiomic inference of gene regulatory networks using SCRIPro

“…The flourishing development of spatial omics enables precise analysis of cellular structures within complex tissues and the spatial interactions between cells. Techniques such as Stereo-seq[21] and STARmap plus[22], have achieved single-cell-level resolution. These methods have significantly enhanced our understanding of gene regulation in specific microenvironments, providing valuable insights into crosstalk between microenvironment interactions and intracellular GRNs.…”

Spatial and temporal profiling of the complement system uncovered novel functions of the alternative complement pathway in brain development

“…MERFISH (Multiplexed Error-Robust Fluorescent in situ Hybridization), a spatial transcriptomic method with single-cell resolution, has emerged as an effective solution (Chen et al, 2015; Moffitt et al, 2018; Moffitt et al, 2016) as it has the demonstrated ability to profile hundreds to thousands of genes, including lowly expressed genes, and from these measurements define, discover, and map cell types in different regions of the mouse and human brain (Allen et al, 2023; Fang et al, 2022; Zhang et al, 2021). Recently, MERFISH and related methods have been extended to define and map cell populations across the entire adult mouse brain (Shi et al, 2023; Yao et al, 2023). By then integrating these measurements with companion single-cell RNA sequencing datasets, the transcriptome-wide gene expression and spatial organization of thousands of neuronal populations has been described.…”