Abstract
BACKGROUND: Peripheral nerve injury can lead to sensory, motor, and autonomic nerve dysfunction, significantly impacting patients' quality of life. Schwann cells (SCs), as key components of the peripheral nervous system, play a crucial role in nerve repair. However, many functionally specialized and flexible SC subtypes remain unidentified. Recent advancements in single-cell transcriptomics have enabled a deeper understanding of SC heterogeneity during peripheral nervous system development. METHODS: In this study, we utilized single-cell transcriptomics to investigate SC heterogeneity in the dorsal root ganglia of both normal and spinal nerve injury mouse models. RESULTS: We identified a novel SC subtype associated with pressure sensation, which we termed stress response related SCs (SRSCs). These cells are terminally differentiated and highly express the pressure-sensing gene Npy. Following peripheral nerve injury, SRSCs function as stimulus receptors, receiving external stimuli and transmitting signals to typical repair SCs via the SPP1 signaling network. This interaction promotes dedifferentiation and facilitates injury repair. CONCLUSION: Our findings enhance the understanding of SC heterogeneity and reveal SRSCs as key players in nerve repair. These insights provide potential targets for developing novel therapeutic strategies for peripheral nerve diseases.