Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease.

Kangli Wang, Weikun Xia, Yingli Gu, Songpeng Zu, Qian Yang, Maria Luisa Amaral, Yaozhi Wang, Allen Wang, Xiang-Dong Fu, William C Mobley, Bing Ren

University of California San Diego, School of Medicine.University of California San Diego, School of Medicine. · pubmed

Paper

Abstract

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 datasets highlights 85 genes consistently differentially expressed with aging and PD. Key genes such as

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Research summary

The study identifies age-associated gene expression changes in the substantia nigra that are linked to Parkinson's disease. This research is relevant as it explores the molecular mechanisms connecting aging and neurodegeneration, potentially addressing root causes of age-related diseases.

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