Fig. 1: Spatial and cell-type profiling of subcortical control and MS tissues.

a, Lesion characterization design (left) and histological assessment (right) of MS lesions with IHC for CD163 and CD68 (myeloid cells) and stains for iron and LFB (myelin). Scale bars, 500 µm (Overview), 100 µm (CD163, CD68, Iron, LFB). b, Study design showing different data modalities and associated metadata. Links between samples indicate that they come from the same tissue block. NA, not available. c, Barplot with number of cell subtypes per main cell type (left), UMAP of integrated snRNA-seq data (n = 103,794, center) and dot plot of averaged z-transformed gene expression of marker genes for each cell type (right). Color corresponds to annotated cell types. d, Spatial panel displaying H&E staining (left), feature plots of cell type deconvolution results (center) and inferred pathway activities (right) in CTRL and MS lesion types. e, Pipeline design using MOFA+ to generate a spatial clustering from the integration of gene expression and deconvoluted cell type proportions (left) and comparison of histopathological areas with the computationally annotated niches between lesion types (right). f, Dot plot of averaged z-transformed gene expression of marker genes for each niche. g, Heatmap of z-transformed cell type proportions for each niche, asterisks indicate significance (adjusted P < 0.05). Min., minimum; max., maximum.