# Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype

**Authors:** Xianfeng Lan, Yanmei Zheng, Yongliang You, Xuejun Wu, Shaojie Wu, Nengfu Chen, Lihong Wang, Wenfu Yang

PMC · DOI: 10.1515/med-2025-1186 · Open Medicine · 2025-05-21

## TL;DR

This study identifies a new type of Schwann cell involved in sensing pressure and aiding nerve repair after injury.

## Contribution

The discovery of stress response related Schwann cells (SRSCs) and their role in nerve repair through the SPP1 signaling network.

## Key findings

- A novel Schwann cell subtype, SRSCs, was identified that highly expresses the pressure-sensing gene Npy.
- SRSCs transmit signals to repair Schwann cells via the SPP1 signaling network after nerve injury.
- SRSCs promote dedifferentiation and injury repair in the peripheral nervous system.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Genes:** NPY (neuropeptide Y) [NCBI Gene 4852]
- **Proteins:** SPP1 (secreted phosphoprotein 1)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** NPY (neuropeptide Y) [NCBI Gene 4852] {aka PYY4}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}
- **Diseases:** peripheral nerve diseases (MESH:D010523), , and autonomic nerve dysfunction (MESH:D005155), spinal nerve injury (MESH:D061227), Peripheral nerve injury (MESH:D059348)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12103108