Single-Cell Sequencing Screening of Biomarkers Associated with Lipophagy in the MPTP Model Mice of Parkinson's Disease.

Abstract

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.