Self-renewing macrophages in dorsal root ganglia contribute to promote nerve regeneration

Resource raw data for manuscript Abstract: Sensory neurons located in dorsal root ganglia (DRG) convey sensory information from peripheral tissue to the brain. After peripheral nerve injury, sensory neurons switch to a regenerative state to enable axon regeneration and functional recovery. This process is not cell autonomous and requires glial and immune cells. Macrophages in the DRG (DRGMacs) accumulate in response to nerve injury, but their origin and function remains unclear. Here we mapped the fate and response of DRGMacs to nerve injury using macrophage depletion, fate-mapping and single-cell transcriptomics. We identified three subtypes of DRGMacs after nerve injury in addition to a small population of circulating bone-marrow-derived precursors. Self-renewing macrophages, which proliferate from local resident macrophages, represent the largest population of DRGMacs. The other two subtypes include microglia-like cells and macrophage-like satellite glial cells (Imoonglia). We show that self-renewing DRGMacs contribute to promote axon regeneration. Using single-cell transcriptomics data and CellChat to simulate intercellular communication, we reveal that macrophages express the neuroprotective and glioprotective ligand prosaposin and communicate with satellite glial cells via the prosaposin receptor GPR37L1. These data highlight that DRGMacs have the capacity to self-renew, similarly to microglia in the CNS and contribute to promote axon regeneration. These data also reveal the heterogeneity of DRGMacs and their potential neuro- and glioprotective roles, which may inform future therapeutic approaches to treat nerve injury.本手稿配套的原始资源数据 摘要：位于背根神经节（dorsal root ganglia, DRG）的感觉神经元负责将外周组织的感觉信号传递至大脑。外周神经损伤发生后，感觉神经元会转变为再生表型，以介导轴突再生与功能修复。该过程并非细胞自主调控，而是依赖神经胶质细胞与免疫细胞的协同参与。背根神经节内的巨噬细胞（DRGMacs）会在神经损伤后发生募集聚集，但其具体起源与功能机制仍有待阐明。本研究借助巨噬细胞耗竭、命运图谱追踪与单细胞转录组学技术，系统解析了DRGMacs在神经损伤后的命运变化与响应特征。研究团队在损伤后的DRGMacs中鉴定出三类亚型，同时还发现了一小群循环来源的骨髓前体细胞。其中，由局部常驻巨噬细胞增殖产生的自我更新型巨噬细胞构成了DRGMacs的主要种群。其余两类亚型分别为类小胶质细胞与巨噬细胞样卫星胶质细胞（Imoonglia）。实验证实，自我更新型DRGMacs可有效促进轴突再生。本研究通过整合单细胞转录组学数据与CellChat细胞通讯模拟工具，揭示巨噬细胞可表达兼具神经保护与胶质保护活性的配体prosaposin，并通过其受体GPR37L1与卫星胶质细胞完成跨细胞通讯。上述数据表明，DRGMacs具备与中枢神经系统（central nervous system, CNS）中小胶质细胞类似的自我更新能力，并可正向调控轴突再生进程。本研究同时揭示了DRGMacs的细胞异质性及其潜在的神经与胶质保护功能，这将为未来开发神经损伤治疗的靶向干预策略提供重要理论依据。