Multiomics profiling of molecular and cellular dynamics of spinal cord injury in a rat [mRNA-seq]

Spinal cord injury (SCI) is a debilitating condition with no effective treatment. The injury triggers a complex cascade of molecular and cellular events that drive both damage and repair processes. To explore these mechanisms, we performed a comprehensive multiomics analysis in a rat compression model of SCI, focusing on the acute phase. Transcriptomic profiling revealed extensive gene dysregulation, highlighting early inflammation, neuronal death, and synaptic dysfunction, followed by the initiation of reparative processes. Cell type composition analysis showed a rapid infiltration of peripheral immune cells, activation of microglia, and loss of neurons, astrocytes, and oligodendrocytes. miRNA profiling uncovered a highly dysregulated miRNA landscape, with the miR-17~92 cluster emerging as a key regulator of neurogenesis, synaptic activity, and cell survival. Integrative miRNA-mRNA-protein analysis identified potential therapeutic targets, including miR-20a, whose inhibition in vitro supported neurogenesis and reduced apoptosis under oxidative stress. Our findings provide new insights into the molecular mechanisms of SCI and highlight miRNAs as potential targets for therapeutic intervention.脊髓损伤（Spinal cord injury, SCI）是一种尚无有效治疗手段的致残性疾病。损伤会触发复杂的分子与细胞级联反应，同时介导损伤进展与修复过程。为探究此类病理机制，本研究在大鼠脊髓压迫性SCI模型中开展了针对急性期的全面多组学分析（multiomics analysis）。转录组分析（Transcriptomic profiling）结果显示存在广泛的基因表达失调，明确了早期炎症、神经元死亡与突触功能障碍，随后启动了修复程序。细胞类型组成分析（Cell type composition analysis）揭示了外周免疫细胞的快速浸润、小胶质细胞激活，以及神经元、星形胶质细胞与少突胶质细胞的丢失。miRNA谱分析（miRNA profiling）发现miRNA表达谱存在高度失调，其中miR-17~92基因簇作为神经发生、突触活动与细胞存活的关键调控因子脱颖而出。整合性miRNA-mRNA-蛋白质组分析（Integrative miRNA-mRNA-protein analysis）鉴定出潜在治疗靶点，包括miR-20a；体外实验证实抑制该靶点可促进神经发生，并减轻氧化应激下的细胞凋亡。本研究结果为脊髓损伤的分子机制提供了全新见解，并凸显了miRNA作为治疗干预潜在靶点的应用价值。