Integrated profiling of single cell epigenomic and transcriptomic landscape of Parkinson's disease mouse brain

Parkinson9s disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons. PD pathogenesis has been largely investigated, but either restricted in bulk level or certain cell type, which hinders the exploration of intercellular interplays. To overcome this, we applied single-nucleus RNA-seq and single cell ATAC-seq on cerebellum, midbrain and striatum of PD mouse and matched control. With 74,493 cells in total, we comprehensively depicted the dysfunctions under PD pathology covering proteostasis, neuroinflammation, calcium homeostasis and extracellular neurotransmitter homeostasis. Besides, by multi-omics approach, we identified putative biomarkers for early stage of PD, based on the relationships between transcriptomic and epigenetic profiles. We located certain cell types that primarily contribute to PD early pathology, narrowing the gap between genotypes and phenotypes. Taken together, our study provides a valuable resource to dissect the molecular mechanism of PD pathogenesis at single cell level, which could facilitate the development of novel methods regarding diagnosis, monitoring and practical therapies against PD at early stage.