Microglial landscape and signaling in spinal cord injury.

Abstract

An integrated bioinformatics data study. This study uses bioinformatics analysis to map the microglial landscape, investigate key signaling pathways, and reveal the molecular mechanisms that facilitate SCI recovery. Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University. 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. 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. 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.