Single-cell brain atlas of Parkinson's disease mouse model.
J Genet Genomics
; 48(4): 277-288, 2021 04 20.
Article
em En
| MEDLINE
| ID: mdl-34052184
ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disease, leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either limited to bulk transcriptomic levels or at certain cell types, which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types. Here, we report the application of single-nucleus RNA-seq on midbrain, striatum, and cerebellum of the α-syn-A53T mouse, a well-established PD mouse model, and matched controls, generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells. Additionally, we comprehensively depicte 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 identify 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 the single-cell resolution, which facilitates the development of novel approaches for diagnosis and therapies against PD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Encéfalo
/
Transcriptoma
/
Proteínas de Filamentos Intermediários
/
Proteínas Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Genet Genomics
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China