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.外周神经包含轴突及其被包裹的胶质细胞——施万细胞（Schwann cells, SC），这类细胞可分为髓鞘型与非髓鞘型（nmSC）。当前学界对周围神经系统（PNS）内其他细胞类群的认知仍较为有限。本研究对健康未患病的啮齿类外周神经系统开展了无偏单细胞转录组表征分析。我们鉴定并独立验证了此前未被充分认识的非髓鞘型施万细胞与神经相关成纤维细胞的新型标志物。此外，我们还发现并表征了两类独特的神经驻留稳态髓系细胞群，其转录特征与中枢神经系统小胶质细胞存在显著差异。在慢性自身免疫性神经炎模型中，稳态髓系细胞的数量被浸润淋巴细胞超越，后者可调控局部细胞间互作组，并在胶质细胞中诱导特异性转录响应。该响应在外周与中枢神经系统胶质细胞间存在部分保守性，由此揭示了神经系统不同区域共有的免疫学特征。综上，本研究鉴定了外周神经系统细胞的新型亚型与细胞类型标志物，以及胶质细胞中诱导产生的部分保守自身免疫模块。