Fig. 7: Spatial transcriptomics reveals immune and neuronal dysregulation in high-seeder PSP cases.

a H&E sections of the four slices of primary motor cortex assayed with Visium spatial transcriptomic. b Marker genes confirm manually annotated cortical layers. c Annotated cortical layers in each slide, white white matter, other colors are the same as in panel d. “Edge” indicates a region of stressed tissue found on the edge of the tissue sample. d Uniform Manifold Approximation and Projection (UMAP) shows annotated layers are transcriptionally distinct. e UMAP confirms successful integration of spatial transcriptomic profiles across slices. f Differentially expressed genes were identified using a negative binomial mixed-effect model, significant genes were identified (<5% FDR) and used for pathway analysis with GSEA. The top 25 significantly (after Benjamini–Hochberg multiple testing correction) enriched Reactome pathways, which overlap with pathways detected through proteomic analysis. Spatial transcriptomic assays were performed once on each of the four independent tissue slices, with internal technical quality control and integrated analysis across slices as described in the Methods. PSP progressive supranuclear palsy, H&E hematoxylin and eosin, Visium 10x Genomics Visium platform, UMAP uniform manifold approximation and projection, DEG differentially expressed gene, FDR false discovery rate, BH Benjamini–Hochberg, GSEA gene set enrichment analysis. LS low seeder, HS high seeder.