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Updated: Sep 18, 2025
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Single-Cell Sequencing Screening of Biomarkers Associated with Lipophagy in the MPTP Model Mice of Parkinson's
Mei-Jun Liu1, Jing-Yi Zhu1, Shi-Yu Han1
1Department of Neurology, Hospital of Chengdu university of TCM, Shier Qiao Road No.39, Chengdu, Sichuan Province, 610072, China.
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.
Insights
This study identifies Ubb, Gapdh, Cox4i1, and Hsp90aa1 as key biomarkers in Parkinson's disease (PD) pathogenesis. Oligodendrocytes and neurons are identified as crucial cell types involved in PD progression.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Parkinson's disease (PD) pathogenesis involves complex mechanisms, with lipophagy's role and specific molecular pathways remaining underexplored.
- Understanding cellular and molecular changes in PD is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of lipophagy in Parkinson's disease using a mouse model.
- To identify novel biomarkers and key cell types involved in PD pathogenesis through single-cell RNA sequencing.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on MPTP-induced Parkinson's disease mouse models.
- Differential gene expression analysis, cell clustering, biomarker screening using CytoNCA, and cell-cell communication analysis were employed.
Main Results:
- scRNA-seq identified distinct cell types, including oligodendrocytes and neurons, with significant alterations in Parkinson's disease models.
- Four genes (Ubb, Gapdh, Cox4i1, Hsp90aa1) were identified as significant biomarkers with differential expression in key cell types.
- Biomarker expression increased at the end of oligodendrocyte and neuron differentiation, suggesting their involvement in disease progression.
Conclusions:
- Ubb, Gapdh, Cox4i1, and Hsp90aa1 are identified as potential biomarkers for Parkinson's disease.
- Oligodendrocytes and neurons are highlighted as critical cell types in the context of PD.
- This research provides new theoretical insights supporting potential therapeutic strategies for Parkinson's disease.
