Fig. 2: Heterogeneity of human nerve-associated immune cells.

A UMAP of 18,436 nuclei representing 35 immune cell (IC) subclusters of 37 human sural nerves. B Feature plots of known endoneurial and epineurial macrophage marker genes. Color encodes gene expression. C Spatial-seq was performed on sural nerve samples from a total of eight patients. Representative spatial-seq images of the macrophage marker MS4A7 and the endoneurial macrophage markers CX3CR1 and TREM2 in the sural nerve of CTRL patient S24. Each dot represents the expression of one transcript, a dotted line marks the perineurium, and a solid line surrounds individual vessels. D Gene ontology term enrichment analysis of marker genes (log₂ fold change > 2, adjusted p-value < 0.001) expressed by the Macro18/LAM cluster in a one vs. all immune cell cluster comparison. Statistical significance was assessed using enrichR (one-sided Fisher’s exact test with p-values adjusted for multiple comparisons using the Benjamini-Hochberg method). E Gene expression of lipid-associated macrophages in the immune cell subclusters. F Stroke-associated myeloid cells (SAMC) from Beuker et al. were projected onto the immune cell clustering. Each red dot denotes a nucleus predicted to be a SAMC. G Representative histological section characterizing Macro18/LAM cluster by co-staining marker genes with myelin and BODIPY (labels neutral lipids). SPP1 encodes osteopontin. Nuclei were stained with DAPI. Stainings were performed on a minimum of two sural nerve sections per patient from a total of three patients.