Single-cell brain atlas of Parkinson's disease mouse model

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:48

Enthalten in:

Journal of genetics and genomics = Yi chuan xue bao - 48(2021), 4 vom: 20. Apr., Seite 277-288

Sprache:

Englisch

Beteiligte Personen:

Zhong, Jixing [VerfasserIn]
Tang, Gen [VerfasserIn]
Zhu, Jiacheng [VerfasserIn]
Wu, Weiying [VerfasserIn]
Li, Ge [VerfasserIn]
Lin, Xiumei [VerfasserIn]
Liang, Langchao [VerfasserIn]
Chai, Chaochao [VerfasserIn]
Zeng, Yuying [VerfasserIn]
Wang, Feiyue [VerfasserIn]
Luo, Lihua [VerfasserIn]
Li, Jiankang [VerfasserIn]
Chen, Fang [VerfasserIn]
Huang, Zhen [VerfasserIn]
Zhang, Xiuqing [VerfasserIn]
Zhang, Yu [VerfasserIn]
Liu, Hongde [VerfasserIn]
Qiu, Xin [VerfasserIn]
Tang, Shengping [VerfasserIn]
Chen, Dongsheng [VerfasserIn]

Links:

Volltext

Themen:

α-syn-A53T
Intermediate Filament Proteins
Journal Article
Muscle Proteins
NF-kappa B
Neuroinflammtion
Parkinson's disease
Pathogenesis
Research Support, Non-U.S. Gov't
Single-nucleus RNA-Seq
Sync protein, mouse

Anmerkungen:

Date Completed 18.01.2022

Date Revised 18.01.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jgg.2021.01.003

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM326008403