Zhang Fa-Li, Li Ai-Ying, Niu Yi-Lin, Zhang Kai, Zhao Ming-Hui, Huang Jiao-Jiao, Shen Wei
College of Life Sciences, Qingdao Agricultural University, Qingdao, China.
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China.
Front Aging Neurosci. 2024 Nov 20;16:1485722. doi: 10.3389/fnagi.2024.1485722. eCollection 2024.
Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by the death of dopamine neurons in the substantia nigra. A large number of studies have focused on dopamine neurons themselves, but so far, the pathogenesis of PD has not been fully elucidated.
Here, we explored the significance of oligodendrocyte precursor cells (OPCs)/oligodendrocytes in the pathogenesis of PD using a bioinformatic approach. WGCNA analysis suggested that abnormal development of oligodendrocytes may play a key role in early PD. To verify the transcriptional dynamics of OPCs/oligodendrocytes, we performed differential analysis, cell trajectory construction, cell communication analysis and hdWGCNA analysis using single-cell data from PD patients. Interestingly, the results indicated that there was overlap between hub genes and differentially expressed genes (DEGs) in OPCs not in oligodendrocytes, suggesting that OPCs may be more sensitive to PD drivers. Then, we used ROC binary analysis model to identify five potential biomarkers, including AGPAT4, DNM3, PPP1R12B, PPP2R2B, and LINC00486.
In conclusion, our work highlights the potential role of OPCs in driving PD.
帕金森病(PD)是一种与年龄相关的神经退行性疾病,其特征是黑质中多巴胺能神经元死亡。大量研究聚焦于多巴胺能神经元本身,但迄今为止,PD的发病机制尚未完全阐明。
在此,我们使用生物信息学方法探讨少突胶质前体细胞(OPCs)/少突胶质细胞在PD发病机制中的意义。加权基因共表达网络分析(WGCNA)表明,少突胶质细胞的异常发育可能在早期PD中起关键作用。为验证OPCs/少突胶质细胞的转录动态,我们使用来自PD患者的单细胞数据进行差异分析、细胞轨迹构建、细胞通讯分析和高密度WGCNA分析。有趣的是,结果表明在OPCs而非少突胶质细胞中,枢纽基因与差异表达基因(DEGs)存在重叠,提示OPCs可能对PD驱动因素更敏感。然后,我们使用ROC二元分析模型鉴定出五个潜在生物标志物,包括AGPAT4、DNM3、PPP1R12B、PPP2R2B和LINC00486。
总之,我们的工作突出了OPCs在驱动PD方面的潜在作用。