Liu Mei-Jun, Zhu Jing-Yi, Han Shi-Yu, Zhu Si-Jia, Yang Dong-Dong
Department of Neurology, Hospital of Chengdu university of TCM, Shier Qiao Road No.39, Chengdu, Sichuan Province, 610072, China.
Mol Neurobiol. 2025 Jun 19. doi: 10.1007/s12035-025-05014-0.
Lipophagy may play an antioxidant and protective role in the pathogenesis of Parkinson's disease (PD). However, the specific mechanism of lipophagy in PD is rarely reported. MPTP model mice brains (PD, n = 3; CON, n = 3) underwent scRNA-seq. Post-QC, cells were clustered and annotated. Differential infiltrated cells (DICs) were identified between PD and CON. DICs were further sub-clustered. DIC-DEGs and DE-LRGs were determined. Overlapping DIC-DEGs and DE-LRGs yielded candidate genes. CytoNCA's five algorithms screened biomarkers. Biomarker expression was compared between PD and CON. Cell-cell communication and pseudotime analyses explored communication and differentiation. In scRNA-seq, 28 distinct clusters were annotated with seven known cell types, including oligodendrocytes, astrocytes, and neurons. Among them, the DICs, oligodendrocytes, and neurons were clustered into six and seven distinct cell subclusters, respectively. Importantly, a total of 241 DIC-DEGs and 664 DEGs were identified, followed by generating 179 candidate genes. Ubb, Gapdh, Cox4i1, and Hsp90aa1 were determined as biomarkers by five algorithms. Notably, the expression levels of four biomarkers were significantly different in oligodendrocytes and neurons between the PD and CON groups. Subsequently, the pseudotime analysis found that the expression of biomarkers was higher at the end of differentiation in both oligodendrocytes and neurons. What is more, the cell crosstalk between the oligodendrocytes and neurons was high in PD and CON groups. Overall, Ubb, Gapdh, Cox4i1, and Hsp90aa1 were mined as biomarkers, and oligodendrocytes and neurons were key cells in PD patients. Our findings provided new theoretical support for PD treatment.
脂质自噬可能在帕金森病（PD）的发病机制中发挥抗氧化和保护作用。然而，脂质自噬在PD中的具体机制鲜有报道。对MPTP模型小鼠脑（PD组，n = 3；对照组，n = 3）进行单细胞RNA测序（scRNA-seq）。质量控制后，对细胞进行聚类和注释。确定PD组和对照组之间的差异浸润细胞（DICs）。对DICs进一步进行亚聚类。确定DIC差异表达基因（DIC-DEGs）和差异表达配体-受体基因（DE-LRGs）。重叠的DIC-DEGs和DE-LRGs产生候选基因。利用CytoNCA的五种算法筛选生物标志物。比较PD组和对照组之间生物标志物的表达。通过细胞间通讯和拟时间分析探索细胞间通讯和分化。在scRNA-seq中，28个不同的聚类被注释为七种已知细胞类型，包括少突胶质细胞、星形胶质细胞和神经元。其中，DICs、少突胶质细胞和神经元分别聚类为六个和七个不同的细胞亚聚类。重要的是，共鉴定出241个DIC-DEGs和664个差异表达基因，随后产生179个候选基因。通过五种算法确定泛素B（Ubb）、甘油醛-3-磷酸脱氢酶（Gapdh）、细胞色素c氧化酶亚基4同工酶1（Cox4i1）和热休克蛋白90α家族成员1（Hsp90aa1）为生物标志物。值得注意的是，在PD组和对照组之间，少突胶质细胞和神经元中四种生物标志物的表达水平存在显著差异。随后，拟时间分析发现，在少突胶质细胞和神经元分化末期，生物标志物的表达均较高。此外，在PD组和对照组中，少突胶质细胞和神经元之间的细胞串扰较高。总体而言，Ubb、Gapdh、Cox4i1和Hsp90aa1被挖掘为生物标志物，少突胶质细胞和神经元是PD患者的关键细胞。我们的研究结果为PD治疗提供了新的理论支持。
