Abstract
Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can shed light on disease mechanisms and progression. Here we introduce STARmap PLUS, a method that combines high-resolution spatial transcriptomics with protein detection in the same tissue section. As proof of principle, we analyze brain tissues of a mouse model of Alzheimer's disease at 8 and 13 months of age. Our approach provides a comprehensive cellular map of disease progression. It reveals a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocyte-like (DAA-like) cells and oligodendrocyte precursor cells (OPCs) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerges mainly in excitatory neurons in the CA1 region and correlates with the local enrichment of oligodendrocyte subtypes. The STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing a tool to pinpoint the molecular and cellular changes underlying pathology.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
