帕金森病人中脑小胶质细胞的亚群分析  

Clustering analysis of microglial subpopulations in midbrain of Parkinson's disease patients

作　　者：刘蓓 何嘉莉 王子艳 黄翔 胡婧[1,2] 钱浩[1,2] LIU Bei;HE JiaLi;WANG ZiYan;HUANG Xiang;HU Jing;QIAN Hao(Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics,Department of Laboratory Medicine,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital,University of Electronic Science and Technology,Chengdu 610072,China;School of Medicine,University of Electronic Science and Technology of China,Chengdu 610054,China;Department of Urology,Sichuan Provincial People's Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu 610072,China)

机构地区：[1]四川省医学科学院·四川省人民医院(电子科技大学附属医院)医学遗传中心,人类疾病基因研究四川省重点实验室,成都610072 [2]电子科技大学医学院,成都610054 [3]四川省医学科学院·四川省人民医院(电子科技大学附属医院)泌尿外科,成都610072

出　　处：《中国科学：生命科学》2023年第9期1298-1309,共12页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:82271276,12102086);四川省科技计划项目(批准号:2022YFS0599,2021YJ0182,2021YJ0196,2020YFS0420)资助。

摘　　要：小胶质细胞是中枢神经系统内最主要的免疫细胞,参与多种神经退行性疾病的病理过程.本研究旨在通过分析帕金森病人中脑小胶质细胞的亚群特征及其随病理过程发生的改变,探索帕金森病治疗的新靶点.利用新近发表的帕金森病人中脑单细胞转录组测序结果,提取小胶质细胞数据,通过与阿尔茨海默病人脑组织中小胶质细胞数据的比对分析,统计各亚群在不同条件下的变化,并分析差异表达基因.研究结果显示,帕金森病人中脑小胶质细胞激活的情况与阿尔茨海默病条件下有显著不同,出现占比增加的亚群并不重合.进一步分析提示,P2RY12,CX3CR1和未折叠蛋白反应信号通路相关的因子等关键蛋白可能与帕金森病人中脑小胶质细胞的增殖有关系.本研究利用病人样本开展的分析说明,不同的神经退行性疾病中,因其不同的病理过程而可能伴随着不同亚群的小胶质细胞的激活,开发针对该类疾病的特异性治疗策略时应系统考量这种差异.As the primary immune cells in the central nervous system,microglia plays a crucial role in various pathological processes of neurodegenerative diseases.This study aims to identify novel therapeutic targets for Parkinson's disease(PD)by analyzing the characteristics of microglial subsets and their alterations associated with neurodegeneration in the midbrain of PD patients.We utilized a recently published dataset to enrich single-cell transcriptomes of microglia from the midbrain of PD patients and conducted clustering analysis,examining changes in each microglial subpopulation under distinct pathological conditions.By comparing the data with that of Alzheimer's disease(AD)patients,we identified differentially expressed genes specific to PD-associated subsets.Our findings reveal distinct activation patterns of microglia in the midbrain of PD patients,with no observed proliferation of ADassociated subpopulations.Further analysis suggests several key proteins,such as P2RY12,CX3CR1,and factors associated with the unfolded protein response,may regulate microglial activation in the midbrain of PD patients.These results highlight that different neurodegenerative diseases may stimulate the activation of distinct microglial subpopulations through diverse pathological conditions.Therefore,understanding the characteristics of microglial subsets is essential for the systematic development of specific therapeutic strategies against PD.

关 键 词：帕金森病 小胶质细胞 细胞亚群 

分 类 号：R742.5[医药卫生—神经病学与精神病学]