Single cell brain atlas of Parkinson’s disease mouse model

Parkinson’s disease (PD) is a neurodegenerative disease leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either restricted in bulk transcriptomic level or at certain cell types, which failed to capture cellular heterogeneity and intrinsic interplays among distinct cell types. To overcome these obstacles, we applied single-nucleus RNA-seq on midbrain, striatum and cerebellum, of α-syn-A53T mouse (a well-established PD model mouse) and matched control, generating the first single cell transcriptomic atlas for PD model mouse brain composed of 46,174 individual cells. Additionally, we comprehensively depicted the dysfunctions in PD pathology, covering the elevation of NF-κB activity, the alteration of ion channel components, the perturbation of protein homeostasis network and the dysregulation of glutamatergic signaling. Notably, we identified a variety of cell types closely associated with PD risk genes. Taken together, our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at single cell resolution, which could hopefully facilitate the development of novel approaches regarding diagnosis and therapies against PD.