目的 利用生物信息学分析结合体内体外实验，探讨类髓磷脂转录因子1(MYT1L)在肌萎缩侧索硬化症（ALS）进展中表达变化的规律及其与神经元退变的关系。 方法 基于GEO数据库GSE106803数据集，比较携带人源超氧化物歧化酶1突变基因（hSOD1G93A)的ALS转基因小鼠与野生型（WT）小鼠脊髓中MYT1L表达差异。选取hSOD1G93A转基因小鼠及其同窝WT对照小鼠，通过Real-time PCR、Western blotting检测小鼠脊髓不同发病时期MYT1L mRNA及蛋白变化，应用免疫荧光双标染色检测MYT1L在发病中期小鼠脊髓内的分布特点及细胞定位。建立hSOD1G93A突变型NSC34细胞（ALS细胞模型）及hSOD1WT型NSC34细胞（WT对照组），通过Real-time PCR、Western blotting、免疫荧光染色检测MYT1L的表达变化及分布。基于GEO数据库GSE76220数据集，筛选ALS患者腰段脊髓运动神经元中MYT1L高表达组和低表达组的差异表达基因（DEGs），并进行基因本体论（GO）功能富集分析。在ALS细胞模型中过表达MYT1L，检测细胞活力和细胞突起改变。 结果 GSE106803数据集中，MYT1L在ALS小鼠脊髓中表达显著下调，动物实验证实，在发病中期、晚期ALS小鼠脊髓组织中MYT1L mRNA和蛋白水平降低。免疫荧光双标记结果显示，与同窝WT组小鼠相比，ALS小鼠腰段脊髓灰质前角神经元中MYT1L表达量降低，星形胶质细胞中MYT1L表达量增加。细胞实验显示，hSOD1G93A突变型NSC34细胞中MYT1L表达量显著低于对照组，MYT1L在ALS细胞模型中胞质、胞核均表达。ALS患者腰段脊髓运动神经元MYT1L高表达组和低表达组的DEGs富集到突触相关功能。过表达MYT1L可提高hSOD1G93A突变型NSC34细胞活力并促进细胞突起生长。 结论 MYT1L异常低表达与ALS病变密切相关，过表达MYT1L可促进神经突生长，对ALS运动神经元具有保护作用。 

Objective To investigate the expression of myelin transcription factor 1-like (MYT1L) during amyotrophic lateral sclerosis (ALS) progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.   Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus (GEO) database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene (hSOD1G93A) compared to the wild-type (WT) mice. hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting. Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease. An ALS cellular model was established using hSOD1G93A mutant NSC34 cells, with hSOD1WT NSC34 cells as controls. MYT1L expression and distribution were assessed in these cells via Real-time PCR, Western blotting, and immunofluorescent staining. Based on the GSE76220 dataset from the GEO database, differentially expressed genes (DEGs) between MYT1L high -and low-expression groups in lumbar spinal motor neurons of ALS patients were identified, followed by Gene Ontology (GO) functional enrichment analysis. MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.   Results In the GSE106803 dataset, MYT1L expression was significantly down-regulated in the spinal cord of ALS mice. Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid- and late-disease stages. Compared to the WT group, MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice, while it increased in astrocytes. In vitro, hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls, with MYT1L localized to both the cytoplasm and nucleus. DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients (GSE76220 dataset) were enriched in synaptic-related functions through GO analysis. Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.    Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis. Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons, suggesting its therapeutic potential.