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Microglial landscape and signaling in spinal cord injury

Spinal Cord volume 63, pages 418–425 (2025)Cite this article

Subjects

Abstract

Study design

An integrated bioinformatics data study.

Objectives

This study uses bioinformatics analysis to map the microglial landscape, investigate key signaling pathways, and reveal the molecular mechanisms that facilitate SCI recovery.

Setting

Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.

Methods

In this study, we performed an integrative bioinformatics analysis of single-cell RNA sequencing (scRNA-seq), spatial transcriptomic (ST), and bulk RNA-seq datasets from the Gene Expression Omnibus (GEO), utilizing R packages (Seurat, DESeq2, limma, GSVA) and the Enrichr platform.

Results

Single-cell and spatial transcriptomic profiling uncovered dynamic shifts in the microglial landscape post-SCI, characterized by the suppression of innate microglial populations alongside the expansion of reactive microglial subsets. Mechanistically, the TGFβ signaling pathway was identified as a critical regulator of innate microglial migration, promoting functional recovery after SCI. Conversely, reactive microglia exhibiting heightened Trem2 expression were found to exacerbate neuroinflammatory responses and drive neural cell death.

Conclusions

These findings collectively indicate that targeting the dual regulatory axis of Trem2-mediated neuroinflammation and TGFβ-driven repair mechanisms may offer a synergistic therapeutic strategy to enhance functional recovery following spinal cord injury.

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Fig. 1: Innate microglial cells are replaced by reactive microglia in SCI.
Fig. 2: TGFβ signaling pathway regulate innate microglial cell migration to improve SCI recovery.
Fig. 3: Reactive microglia contribute to the neuroinflammatory response and positive regulate the neural cell death in SCI.

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Data availability

Data sources and handling are described in the Materials and Methods. The source code is proprietary but available upon request for non-commercial use by contacting Yifeng Sun at syf498054232@163.com.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81702667). Beijing Tsinghua Changgung Hospital Fund (Grant No. 202510S004), China Postdoctoral Science Foundation (Grant No.8206300728).

Author information

Authors and Affiliations

  1. Department of Spine Surgery, Yantaishan Hospital, Binzhou Medical University, 10087 Science and Technology Avenue, Yantai, Shandong, 264003, P.R. China

    Qingsheng Zhou

  2. Department of Catheter room, Tianjin Chest Hospital, Tianjin, 300222, P. R. China

    Jianchao Liu

  3. MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, China

    Qiongxuan Fang

  4. Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, PR China

    Chunming Zhang & Wei Liu

  5. Orthopaedic and Sports Medicine Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

    Yifeng Sun

Authors
  1. Qingsheng Zhou
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  2. Jianchao Liu
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  5. Wei Liu
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Contributions

YS conceived the study and generated figures and wrote the manuscript, QZ collected and analysed the data, QF performed part of the data analysis and was responsible for manuscript revision, JL performed a part of data analysis. CZ and WL help to generated Figures. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Qiongxuan Fang or Yifeng Sun.

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Competing interests

The authors declare no competing interests.

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This is a bioinformatic analysis; therefore, ethics approval and consent to participate are not applicable.

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Cite this article

Zhou, Q., Liu, J., Fang, Q. et al. Microglial landscape and signaling in spinal cord injury. Spinal Cord 63, 418–425 (2025). https://doi.org/10.1038/s41393-025-01103-y

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