SFN 2021 Poster: Molecular Atlassing with MERSCOPE

Biological systems are comprised of numerous cell types, intricately organized to form functional tissues and organs. Building molecular atlases to fully understand the structure and function of each cell within the brain is now a key aspect of neuroscience research. Atlas initiatives using single-cell RNA sequencing can characterize cell types based on their RNA expression profiles. However, the tissue organization is lost when cells are dissociated for single-cell sequencing, making it difficult to study how the cellular heterogeneity is contributing to the function of the tissue. Furthermore, accurately characterizing each cell within the brain is challenging due to the low expression of many functionally important genes such as nonsensory G-Protein coupled receptors (GPCRs). A true spatial transcriptomics technology with high detection efficiency and single molecule resolution is required to build accurate and complete molecular atlases. Vizgen’s in situ genomics platform MERSCOPE™ enables the direct profiling of the spatial organization of intact tissue with subcellular resolution. MERSCOPE is built on multiplexed error robust in situ hybridization (MERFISH) technology that uses combinatorial labeling, sequential imaging, and error-robust barcoding to provide the highest detection efficiency and resolution available for spatial genomics. In a single experiment, hundreds of thousands of cells can be spatially profiled with high accuracy and reproducibility. To demonstrate the power of MERSCOPE, we mapped 483 genes across three full mouse brain coronal slices. We constructed a panel of canonical cell type markers and nonsensory GPCRs to spatially profile nonsensory GPCR expression across the brain with cellular context. Nonsensory GPCRs in the brain mediate signaling and may play vital roles behind brain aging and neurodegenerative disorders but are difficult to analyze. Our experiment successfully detected multiple lowly expressed GPCRs including Oxtr, Tshr, and Insr. The mouse brain receptor map demonstrates MERSCOPE as a leading tool for molecular atlassing, enabling scientists to find greater insights into healthy versus diseased tissue.