High-Dimensional Multi-omic Mapping of Post-Mortem Human Brain Using Iterative Indirect Immunofluorescence Imaging on Xenium-Processed Tissues
Spatial transcriptomics approaches provide crucial insights into gene expression distribution within intact tissue architecture, but they encounter limitations in detecting morphologically complex cell types, assessing their spatial associations with pathology, and accurately annotating cell types using RNA data alone. Therefore, we developed a robust post-processing workflow integrating Xenium…
Spatial transcriptomics has proven invaluable for understanding gene expression patterns within intact tissue structure. However, these methods are limited when it comes to identifying intricate cellular structures, linking their spatial relationships to pathology, and precisely identifying cell types based solely on RNA data. To overcome these challenges, a team of researchers created a refined post-processing workflow that combines Xenium spatial technology with iterative indirect immunofluorescence imaging (4i) on formalin-fixed paraffin-embedded (FFPE) human brain tissue.
This innovative protocol, detailed in the study, facilitates multi-omic tissue mapping, allowing for a more in-depth examination of pathological microenvironments defined by the spatial arrangement of neuropathological markers and the presence of specific cell populations. The researchers put their method to the test by analyzing calcarine cortex tissue sections exhibiting cerebral amyloid angiopathy (CAA) alongside amyloid plaques and tau pathology.
The outcome was a 15-plex image, providing a comprehensive view of the intricate pathological microenvironment.
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