Single-cell brain atlas of Parkinson's disease mouse model
Single-cell brain atlas of Parkinson's disease mouse model
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帕金森病小鼠模型的单细胞脑图谱
DOI：
10.1016/j.jgg.2021.01.003
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发表时间：
2021
影响因子：
5.9
通讯作者：
Chen Dongsheng
中科院分区：
文献类型：
--
作者：
Zhong Jixing;Tang Gen;Zhu Jiacheng;Wu Weiying;Li Ge;Lin Xiumei;Liang Langchao;Chai Chaochao;Zeng Yuying;Wang Feiyue;Luo Lihua;Li Jiankang;Chen Fang;Huang Zhen;Zhang Xiuqing;Zhang Yu;Liu Hongde;Qiu Xin;Tang Shengping;Chen Dongsheng
帕金森病（PD）是一种神经退行性疾病，会导致运动执行功能受损。尽管对帕金森病的发病机制已开展大量研究，但这些研究要么局限于整体转录组水平，要么仅针对某些特定细胞类型，未能全面捕捉细胞的异质性以及不同细胞类型之间内在的相互作用。在此，我们报告了对α - 突触核蛋白A53T小鼠（一种成熟的帕金森病小鼠模型）及其匹配的对照小鼠的中脑、纹状体和小脑进行单核RNA测序的应用情况，生成了首个由46,174个单个细胞组成的帕金森病模型小鼠大脑单细胞转录组图谱。此外，我们全面描绘了帕金森病病理过程中的功能障碍，包括核因子 - κB（NF - κB）活性升高、离子通道成分改变、蛋白质稳态网络紊乱以及谷氨酸能信号传导失调。值得注意的是，我们鉴定出多种与帕金森病风险基因密切相关的细胞类型。综上所述，我们的研究为在单细胞分辨率下系统剖析帕金森病发病机制的分子机制提供了宝贵资源，有助于开发针对帕金森病的新型诊断和治疗方法。
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 a-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-kB 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.