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- Title
Single-cell sequencing of the substantia nigra reveals microglial activation in a model of MPTP.
- Authors
Qing Liu; Ziyu Liu; Wenmeng Xie; Yibo Li; Hongfang Wang; Sanbing Zhang; Wenyu Wang; Jiaxin Hao; Dandan Geng; Jing Yang; Lei Wang
- Abstract
Background: N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. Methods: Single-nucleus RNA sequencing was performed in the Substantia Nigra (SN) of MPTP mice. UMAP analysis was used for the dimensionality reduction visualization of the SN in the MPTP mice. Known marker genes highly expressed genes in each cluster were used to annotate most clusters. Specific Differentially Expressed Genes (DEGs) and PD risk genes analysis were used to find MPTP-associated cells. GO, KEGG, PPI network, GSEA and CellChat analysis were used to reveal cell type-specific functional alterations and disruption of cell-cell communication networks. Subset reconstruction and pseudotime analysis were used to reveal the activation status of the cells, and to find the transcription factors with trajectory characterized. Results: Initially, we observed specific DEGs and PD risk genes enrichment in microglia. Next, We obtained the functional phenotype changes in microglia and found that IGF, AGRN and PTN pathways were reduced in MPTP mice. Finally, we analyzed the activation state of microglia and revealed a pro-inflammatory trajectory characterized by transcription factors Nfe2l2 and Runx1. Conclusion: Our work revealed alterations in microglia function, signaling pathways and key genes in the SN of MPTP mice.
- Subjects
PARKINSON'S disease &; genetics; RNA analysis; RISK assessment; BIOLOGICAL models; RESEARCH funding; CELL communication; NEUROGLIA; GENETIC markers; PARKINSON'S disease; TRANSCRIPTION factors; CELLULAR signal transduction; MICE; BRAIN stem; PYRIDINE; ANIMAL experimentation; GENE expression profiling; DATA analysis software; SEQUENCE analysis; GENETIC testing; PHENOTYPES; DISEASE risk factors
- Publication
Frontiers in Aging Neuroscience, 2024, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2024.1390310