AGBT 2024 Poster: Unveiling Brain Complexity with the MERSCOPE® Platform Using 1000-plex Gene Panels: Insights into Healthy and Diseased States

Abstract: 

The neuronal system consists of various molecularly unique cell types arranged into different anatomical structures. Over the past decade, single-cell sequencing has made considerable strides in elucidating the cell heterogeneity of the nervous system. However, most sequencing-based methodologies require cell dissociation, thus posing challenges to directly linking the molecular characteristics of analyzed cells to their anatomical and functional properties. Recently, spatially resolved genomic technologies enable the probing of molecular profiles, such as gene and protein expression, with subcellular precision while maintaining intact tissue context. Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH) stands at the forefront of spatial transcriptomics, enabling comprehensive mapping of cellular composition and spatial organization within many brain structures.1 In this study, we showcase the capabilities of the Vizgen® MERSCOPE® Platform—an end-to-end solution for MERFISH technology—in deciphering the molecular and cellular features of both mouse and human brain tissue under physiological and pathological conditions. We leveraged the vast gene repertoire of a 960-plex gene panel to achieve unprecedented resolution in neuronal and non-neuronal cell types across disparate mouse brain regions, enabling the molecular and cellular features underpinning various anatomical structures to be uncovered.* Moreover, the integration of molecular and spatial information derived from the same tissue facilitated an in-depth understanding of cell-type-specific signaling and regulatory mechanisms. Furthermore, to understand the pathogenesis of Alzheimer’s Disease (AD) we conducted a spatial multiomics imaging assay on MERSCOPE, concurrently measuring gene expression and protein staining in human brain samples. This enabled us to identify cell-type-specific molecular and cellular adaptations, highlighting a spatially dependent response associated with the disease. In summary, the application of the MERSCOPE Platform not only allows us to understand the spatial organization and interaction of different cell types in the brain, but also sheds light on the fundamental processes of neurobiology and the complex alterations occurring in neurodegenerative diseases such as AD.

*RUO only, not approved for diagnostic or therapeutic purposes.