TY  - JOUR
A1  - Wang, Kangli
A1  - Xia, Weikun
A1  - Gu, Yingli
A1  - Zu, Songpeng
A1  - Yang, Qian
A1  - Amaral, Maria Luisa
A1  - Wang, Yaozhi
A1  - Wang, Allen
A1  - Fu, Xiang-Dong
A1  - Mobley, William C.
A1  - Ren, Bing
T1  - Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
Y1  - 2026/03/04 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.281113.125 
UR  - http://genome.cshlp.org/content/early/2026/03/26/gr.281113.125.abstract 
N2  - Parkinson's disease (PD) is a prevalent neurodegenerative disorder predominantly affecting individuals over 60. Its motor symptoms stem from the deterioration of dopaminergic neurons within the substantia nigra. Despite aging being a significant risk factor, the specific mechanisms linking aging and PD pathology remain unclear. Leveraging advancements in single-cell genomics, this study utilizes single-nucleus multiome sequencing to capture transcriptomic and epigenetic profiles from 40,125 cells across the lifespan of the mouse substantia nigra. Our analysis pinpoints age-associated changes at a cell type–specific level, revealing a subset of genes that increasingly express with age and are enriched in PD-related pathways, notably in oligodendrocytes at late aging stages. Integration with five public PD single-cell RNA-seq data sets highlights 85 genes consistently differentially expressed with aging and PD. Key genes such as Hsp90aa1 and Hsp90ab1 are upregulated at late aging stages in oligodendrocytes, microglia, and glutamatergic neurons. Additionally, Apoe in microglia and genes related to protein folding in oligodendrocytes are upregulated at late aging stages, whereas genes involved in myelination are downregulated at early aging stages in oligodendrocyte. Our multiomic atlas underscores the substantial regulatory network changes during aging that may predispose to PD, providing valuable insights for furthering understanding of PD pathogenesis and potential therapeutic targets. 
ER  -