Transcriptomic patterns of dermal Schwann cell reactivity

Neuropathic pruritus may lead to significant impairment of quality of life. A role of Schwann cells in modulating pain or pruritus has been suggested. In pilot experiments, we showed the feasibility of subepidermal Schwann cell mapping by immunohistochemistry in relation to their axons. Utilizing single-nucleus RNA-seq (snRNA-seq) we could identify Schwann cell subtypes and decode their subtype-specific transcriptomic signatures.

In this project, we will investigate Schwann cell morphology and protein expression in itch and pain, aiming at a deeper understanding of Schwann cell related pathways in the skin in well-defined and matched subgroups of patients. PNP patients with pain or itch as the sole complaint, will be recruited and carefully assessed by clinical measurements. For comparison, we will include patients with brachioradial pruritus, and we will receive skin samples of patients with psoriasis from collaborating project #5. We will then identify and characterize groups of PNP patients with itch, pain and high pain sensitivity upon C-fiber stimulation, aiming at understanding their psychophysical characteristics and at selecting homogenous samples to be used in high-throughput transcriptomic technologies. Next, oligonucleotide-tagged antibody multiplex snRNA-seq will allow us to analyze cell type-specific gene expression from cryo-preserved skin biopsy samples obtained from clinical cohorts. By further in-depth bioinformatic analysis, we will be able to decode the transcriptome profiles of cutaneous Schwann cells between the different clinical entities and define molecular traits of homeostatic and reactive Schwann cells. Multiplex RNA in situ mapping will then be used as an additional method to map back levels of Schwann cell subtype reactivity to the skin and the underlying tissue microenvironment in control and disease samples. We hypothesize that specific Schwann cell characteristics relative to itch or pain will help better understand their role in relation to axon pathology and the clinical phenotype of the patients.