Extended Data Fig. 6: Spatial transcriptomic analysis of CD68 pos myeloid cells in BRL lesion rims, mixed lesion rims and active lesion centers as compared to normal appearing white matter (NAWM).
a, Example of a BRL lesions stained for CD68 (yellow) and the oligodendroglial marker TPPP/p25 (red) and nuclear staining (SYTO83, blue) in the left panel. In the right panel, demonstration of selection masks (green, arrows) used to identify CD68+ myeloid cells for spatial transcriptomic analysis. b, VENN diagram of GO terms (each lesion type compared to respective NAWM) of all three lesion types. c, Spearman correlation of DEG between all lesion types and NAWM. d, Volcano plots of DEGs in BRL CD68+ myeloid cells versus mixed lesion CD68+ myeloid cells (upper panel) as well as of DEG in BRL CD68+ cells versus active lesion CD68+ myeloid cells (lower panel), and respective NAWM. Blue dots indicate genes with significant differential enrichment between conditions (adjusted p value < 0.05); relevant genes of interest are annotated. e, Heatmap visualization of gene set enrichment analysis (GSEA) of the three lesion types with published transcriptomic signatures, with Gene Ontology (GO) Biological Processes (BP) gene sets as signatures. Only signatures with significance in comparison to at least one lesion type are depicted. f, Expression of three genes of interest in all three lesion types and in NAWM, depicted are Bruton tyrosine kinase (BTK), CD40L, and RIPK1.
