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

• 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
• 机 构: School of Biological Science & Medical Engineering,Southeast University,Nanjing 210096,China;BGI-She
• 出 处: 遗传学报
• 发表日期: 2021年4期
• 关键词: Parkinson's disease α-syn-A53T Single-nucleus RNA-Seq Pathogenesis Neuroinf

Parkinson\'s disease (PD) is a neurodegenerative disease,leading to the impairment of movement execu-tion.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.Addi-tionally,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 mo-lecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.