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

Journal of Genetics and Genomics 2021年第4期48卷 277-288页

作者： Jixing Zhong Gen tang Jiacheng Zhu Weiying Wu Ge Li Xiumei Lin Langchao Liang Chaochao Chai Yuying Zeng Feiyue Wang Lihua Luo Jiankang Li Fang Chen Zhen Huang Xiuqing Zhang Yu Zhang Hongde Liu Xin Qiu Shengping tang Dongsheng Chen School of Biological Science&Medical Engineering Southeast UniversityNanjing 210096China BGI-Shenzhen Shenzhen 518083China Shenzhen Children's Hospital Shenzhen 518083China BGI Education Center University of Chinese Academy of SciencesShenzhen 518083China Department of Neurobiology NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Brain Science and Brian MedicineAnd the MOE Frontier Science Center for Brain Research and Brain-Machine IntegrationZhejiang University School of MedicineHangzhou 310012China Guangdong Provincial Key Laboratory of Laboratory Animals Guangdong Laboratory Animals Monitoring InstituteGuangzhouGuangdong 510663China MGI BGI-ShenzhenShenzhen 518083China Life Science College Fujian Normal UniversityFuzhou 350108China Key Laboratory of Special Marine Bio-resources Sustainable Utilization of Fujian Province Fuzhou 350108China

Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement *** 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 ***,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 t 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 ***,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic ***,we identify a variety of cell types closely associated with PD risk *** 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.

关键词： Parkinson’s disease α-syn-a53t Single-nucleus RNA-Seq Pathogenesis Neuroinflammtion

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