Fig. 1: Defining the species-specific cellular landscape of human peripheral nerves.

A Schematic overview of the experimental procedure. Sural nerve biopsies were collected from 33 polyneuropathy (PNP) patients and four controls (CTRL) from three German centers (Essen, Münster, Würzburg) and processed by single-nucleus RNA-sequencing (snRNA-seq). In addition, subcellular spatial transcriptomics (spatial-seq) was performed in a subgroup of eight patients. All 37 tissues were histologically characterized by quantifying myelin thickness (g-ratio), number of intactly myelinated axons, and axon diameters. Perineurium thickness was measured in 12 CIDP and 18 CTRL patients using immunohistochemistry (IHC) targeting epithelial membrane antigen. Markers were confirmed using RNA in situ hybridization (RNA-ISH) and immunofluorescence (IF). B UMAP of 365,708 high-quality nuclei from 37 human sural nerves, showing 24 main clusters. C Schematic depicting if marker genes of human myelinating Schwann cells (mySC), non-myelinating Schwann cells (nmSC), and perineurial cells (periC) found in this dataset using snRNA-seq and spatial-seq were detected when reanalyzing published rodent datasets (Yim et al., Gerber et al., Wolbert et al., Supplementary Data 4–6) when performing RNA-ISH/IF histology in rodents and whether these markers were previously described in rodent or human literature. D, E Spatial-seq was performed on sural nerve samples from a total of eight patients. Representation sections from CTRL patient S24 are shown. D Representative section of an H&E staining overlaid with spatial-seq showing predicted clusters in spatial-seq of a sural nerve cross-section. Each dot represents one cell. E Representative spatial-seq images of selected genes expressed in perineurial cells. F Immunofluorescence staining was performed on a minimum of two sural nerve sections per patient from a total of four patients. Representative immunofluorescence image showing CXCL14 staining in perineurial cells from CIAP patient S10. The dotted line marks the perineurium. G, H Spatial-seq was performed on sural nerve samples from a total of eight patients. Representation sections from CTRL patient S24 are shown. Representative spatial-seq images of selected genes expressed in (G) cells of the blood nerve barrier (BNB) and (H) in mySC (blue highlight) and nmSC (red highlight). Each dot represents the expression of one transcript, a dotted line marks the perineurium, and a solid line surrounds individual vessels. Icons were created in BioRender. Meyer zu Hörste, G. (2025) https://BioRender.com/l74v346.