Microglial landscape and signaling in spinal cord injury.

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Spinal cord Pub Date : 2025-07-07 DOI:10.1038/s41393-025-01103-y

Qingsheng Zhou, Jianchao Liu, Qiongxuan Fang, Chunming Zhang, Wei Liu, Yifeng Sun

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引用次数: 0

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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脊髓损伤中的小胶质细胞景观和信号传导。

研究设计：综合生物信息学数据研究。目的：本研究利用生物信息学分析绘制小胶质细胞景观，研究关键信号通路，揭示促进脊髓损伤恢复的分子机制。单位：北京清华长庚医院，清华大学临床医学院。方法：在本研究中，我们利用R软件包（Seurat、DESeq2、limma、GSVA）和enrichment平台，对来自基因表达Omnibus （GEO）的单细胞RNA测序（scRNA-seq）、空间转录组学（ST）和大量RNA-seq数据集进行了综合生物信息学分析。结果：单细胞和空间转录组分析揭示了脊髓损伤后小胶质细胞景观的动态变化，其特征是先天小胶质细胞群受到抑制，同时反应性小胶质细胞亚群扩大。机制上，TGFβ信号通路被认为是先天小胶质细胞迁移的关键调节因子，促进脊髓损伤后的功能恢复。相反，Trem2表达升高的反应性小胶质细胞会加剧神经炎症反应并驱动神经细胞死亡。结论：这些发现共同表明，靶向trem2介导的神经炎症和tgf β驱动的修复机制的双调控轴可能提供一种协同治疗策略，以增强脊髓损伤后的功能恢复。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Spinal cord 医学-临床神经学

CiteScore

4.50

自引率

9.10%

发文量

142

审稿时长

2 months

期刊介绍： Spinal Cord is a specialised, international journal that has been publishing spinal cord related manuscripts since 1963. It appears monthly, online and in print, and accepts contributions on spinal cord anatomy, physiology, management of injury and disease, and the quality of life and life circumstances of people with a spinal cord injury. Spinal Cord is multi-disciplinary and publishes contributions across the entire spectrum of research ranging from basic science to applied clinical research. It focuses on high quality original research, systematic reviews and narrative reviews. Spinal Cord''s sister journal Spinal Cord Series and Cases: Clinical Management in Spinal Cord Disorders publishes high quality case reports, small case series, pilot and retrospective studies perspectives, Pulse survey articles, Point-couterpoint articles, correspondences and book reviews. It specialises in material that addresses all aspects of life for persons with spinal cord injuries or disorders. For more information, please see the aims and scope of Spinal Cord Series and Cases.