Xin Tang

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 brain 1,2 , but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS 3,4 , to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm 3 , 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 atlas 1 , imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB 5,6 . 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.

Nanoscale materials are now attracting a great deal of attention for biomedical applications. Conjugated polymer nanoparticles have remarkable photophysical properties that make them highly advantageous for biological fluorescence imaging. We report on conjugated polymer nanoparticles with phenylboronic acid tags on the surface for fluorescence detection of neurotransmitter dopamine in both living PC12 cells and brain of zebrafish larvae. The selective enrichment of dopamine and fluorescence signal amplification characteristics of the nanoparticles show rapid and high-sensitive probing such neurotransmitter with the detection limit of 38.8 nM, and minimum interference from other endogenous molecules. It demonstrates the potential of nanomaterials as a multifunctional nanoplatform for targeting, diagnosis, and therapy of dopamine-relative disease.