Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity

重新定义健康和自身免疫中周围神经细胞的异质性

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作者:Jolien Wolbert, Xiaolin Li, Michael Heming, Anne K Mausberg, Dagmar Akkermann, Clara Frydrychowicz, Robert Fledrich, Linda Groeneweg, Christian Schulz, Mark Stettner, Noelia Alonso Gonzalez, Heinz Wiendl, Ruth Stassart, Gerd Meyer Zu Hörste

Abstract

Peripheral nerves contain axons and their enwrapping glia cells named Schwann cells (SCs) that are either myelinating (mySCs) or nonmyelinating (nmSCs). Our understanding of other cells in the peripheral nervous system (PNS) remains limited. Here, we provide an unbiased single cell transcriptomic characterization of the nondiseased rodent PNS. We identified and independently confirmed markers of previously underappreciated nmSCs 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, indicating common immunological features across different parts of the nervous system. Our study thus identifies subtypes and cell-type markers of PNS cells and a partially conserved autoimmunity module induced in glia cells.

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