scRNA-seq generates a molecular map of emerging cell subtypes after sciatic nerve injury in rats

Patients with peripheral nerve injury, viral infection or metabolic disorder often suffer neuropathic pain due to inadequate pharmacological options for relief. Developing novel therapies has been challenged by incomplete mechanistic understanding of the cellular microenvironment in sensory nerve that trigger the emergence and persistence of pain. In this study, we report a high resolution transcriptomics map of the cellular heterogeneity of naïve and injured rat sensory nerve covering more than 110,000 individual cells. Annotation reveals distinguishing molecular features of multiple major cell types totaling 45 different subtypes in naïve nerve and an additional 23 subtypes emerging after injury. Ligand-receptor analysis revealed a myriad of potential targets for pharmacological intervention. This work forms a comprehensive resource and unprecedented window into the cellular milieu underlying neuropathic pain and demonstrates that nerve injury is a dynamic process orchestrated by multiple cell types in both the endoneurial and epineurial nerve compartments.外周神经损伤、病毒感染或代谢紊乱患者常因缺乏有效的镇痛药物治疗方案，而遭受神经病理性疼痛（neuropathic pain）的困扰。由于对触发疼痛发生与维持的感觉神经细胞微环境机制认知不足，开发新型治疗手段一直面临挑战。本研究报道了未损伤（naïve）与损伤状态大鼠感觉神经的细胞异质性高分辨率转录组学（high resolution transcriptomics）图谱，涵盖超过11万个单个细胞。细胞注释结果显示，未损伤神经中共计45种不同亚型的多种主要细胞类型，各自具备独特的分子特征；损伤后又新增了23种细胞亚型。配体-受体（ligand-receptor）分析揭示了大量可用于药物干预的潜在靶点。本研究构建了解析神经病理性疼痛潜在细胞微环境的综合资源库与前所未有的研究窗口，并证实神经损伤是一个由神经内膜（endoneurial）与神经外膜（epineurial）区域内多种细胞协同调控的动态过程。