Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity

Peripheral nerves contain axons and their enwrapping glia cells named Schwann cells (SC) that are either myelinating or non-myelinating (nmSC). Our understanding of other cells in the peripheral nervous system (PNS) remains limited. Here, we provide an unbiased single-cell transcriptomic characterization of the non-diseased rodent PNS. We identified and independently confirmed novel markers of previously underappreciated nmSC and nerve-associated fibroblasts. We also found and characterized two distinct populations of nerve-resident homeostatic myeloid cells that transcriptionally differed from central nervous system microglia. In a model of chronic autoimmune neuritis, homeostatic myeloid cells were outnumbered by infiltrating lymphocytes which modulated the local cell-cell interactome and induced a specific transcriptional response in glia cells. This response was partially shared between the peripheral and central nervous system glia identifying common immunological features across different parts of the nervous system. Our study thus identifies novel subtypes and cell-type markers of PNS cells and a partially conserved autoimmunity module induced in glia cells. Overall design: Single cell RNA sequencing of undiseased C57BL/6 mice and naive Lewis rats to explore the healthy PNS. ScRNA-seq of NOD control and ICAM-1-/-NOD mice was performed to analyze chronic autoimmune neuritis.