Page 51 - 南京医科大学自然版

第45卷第4期 南京医科大学学报（自然科学版）
2025年4月 Journal of Nanjing Medical University（Natural Sciences） ·487 ·

·基础研究·

亨廷顿舞蹈症中星形胶质细胞转录异质性分析

陈贝宁 ，杨清湖 ，袁增强 ，郭 兴 1*
1
3*
2，3
南京医科大学基础医学院神经生物学系，江苏 南京 211166；延安大学生命科学学院多肽药物研究中心//陕西省区域生物
1 2
资源保护与利用工程技术研究中心，陕西 延安 716000；军事科学院军事医学研究院军事认知与脑科学研究所，北京
3
100850

［摘 要］ 目的：解析亨廷顿舞蹈症（Huntington’s disease，HD）病程中小鼠大脑内星形胶质细胞活化状态及转录异质性，筛选
和鉴定HD病程相关的核心基因。方法：利用免疫荧光考察HD病程早期和后期星形胶质细胞的激活情况，采用RT⁃qPCR分析
星形胶质细胞激活表型；利用单细胞解离和磁珠分选技术分离小鼠脑星形胶质细胞，进行转录组学测序；结合生物信息学分
析，分别对HD早期和后期转录组学数据进行差异表达基因（differentially expressed genes，DEG）及基因本体论（Gene Ontology，
GO）功能富集分析；筛选HD病程相关基因进行蛋白质相互作用（protein⁃protein interaction，PPI）网络分析，并验证核心基因的
表达。结果：在HD病程后期，星形胶质细胞转变为A1型反应性星形胶质细胞；病程早期，HD小鼠星形胶质细胞的差异基因
主要与突触间隙和突触结构维持等突触相关功能有关，而病程后期则主要涉及趋化活性、信号转导和细胞响应等功能；最后，
HD病程中星形胶质细胞的核心基因功能主要体现在血管发生、RNA剪接与代谢以及肌肉运动方面。结论：HD病程早期星形
胶质细胞影响神经元发育和突触形成，病程后期星形胶质细胞转变为具有神经毒性的A1型反应性星形胶质细胞；排除衰老过
程影响的星形胶质细胞异质性基因可作为HD病理进展和预测的有效分子标志物，这有望为HD早期发现和诊疗提供新的实
验证据。
［关键词］ 亨廷顿舞蹈症；星形胶质细胞；转录组学
［中图分类号］ R742.2 ［文献标志码］ A ［文章编号］ 1007⁃4368（2025）04⁃487⁃12
doi：10.7655/NYDXBNSN241284

The transcriptional heterogeneity of astrocytes in Huntington’s disease
1
3*
2，3
CHEN Beining ，YANG Qinghu ，YUAN Zengqiang ，GUO Xing 1*
1 Department of Neurobiology，School of Basic Medical Sciences，Nanjing Medical University，Nanjing 211166；School
2
of Life Science & Research Center for Natural Peptide Drugs，Shaanxi Engineering & Technological Research Center
for Conservation & Utilization of Regional Biological Resources，Yan’an University，Yan’an 716000；Institute of
3
Military Cognition and Brain Sciences，Academy of Military Medical Sciences，Academy of Military Sciences，Beijing
100850，China

［Abstract］ Objective：To elucidate the activation status and transcriptional heterogeneity of astrocytes in the mouse brain during
Huntington’s disease（HD）progression，and screen and identify differentially expressed molecules on the key issue. Methods：
Immunofluorescence was employed to examine the transformation of HD astrocytes into reactive astrocytes at both the early and late
stages of the disease，and this transformation was then verified by RT ⁃ qPCR；Single ⁃ cell dissociation and magnetic bead sorting
techniques were utilized to isolate astrocytes from mouse brains for subsequent transcriptome sequencing；Bioinformatics analysis was
conducted to identify differentially expressed genes（DEGs）and perform gene ontology（GO）analysis on the transcriptome data from
the early and late stages of HD；Genes related to HD progression were selected for protein⁃protein interaction（PPI）network analysis，

and the expression of core genes were validated. Results：In the late stage of HD，astrocytes transformed into A1 ⁃ type reactive
astrocytes；In the early stage of the disease，DEGs in HD mouse astrocytes were predominantly associated with synaptic functions，such

［基金项目］ 国家自然科学基金（82230042，82371260）
∗
通信作者（Corresponding author），E⁃mail：guox@njmu.edu.cn（ORCID：0000⁃0002⁃0216⁃0310）；zqyuan@bmi.ac.cn（ORCID：0000⁃
0001⁃5739⁃2867）