Microglia Mediate the Occurrence and Development of Alzheimer's Disease Through Ligand-Receptor Axis Communication.
Microglia Mediate the Occurrence and Development of Alzheimer's Disease Through Ligand-Receptor Axis Communication.
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小胶质细胞通过配体-受体轴通讯介导阿尔茨海默病的发生和发展
DOI：
10.3389/fnagi.2021.731180
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发表时间：
2021
影响因子：
4.8
通讯作者：
Zou D
中科院分区：
文献类型：
--
作者：
Jian C;Wei L;Mo R;Li R;Liang L;Chen L;Zou C;Meng Y;Liu Y;Zou D
阿尔茨海默症（Alzheimer’s disease，AD）是一种常见的神经退行性疾病。其发病机制主要有：其发病隐匿，进展缓慢，难以诊断。此外，其潜在的分子和细胞机制仍不清楚。在本研究中，对48例AD患者前额皮质的单细胞RNA测序（scRNA-seq）数据进行了聚类分析。每个样本模块都被鉴定为特定的AD细胞类型，鉴定了8种主要的脑细胞类型，并通过伪时间分析进一步探索了每种细胞类型的功能障碍性演变。采用相关分析探讨AD细胞类型与病理特征的关系。特别地，通过细胞通讯分析研究了AD患者中神经元和神经胶质细胞之间的细胞间通讯。在患者中，神经元细胞和神经胶质细胞与病理特征显著相关，并且神经胶质细胞似乎通过配体-受体轴通讯在AD的发生发展中发挥关键作用。使用五种类型的模型：logistic回归、多变量logistic回归、最小绝对收缩和选择算子（LASSO）和支持向量机（SVM）来鉴定参与这两种细胞类型之间的通信的标记基因。LASSO模型确定CXCR 4、EGFR、MAP 4K 4和IGF 1 R为该通讯中的关键基因。我们的研究结果支持了小胶质细胞通过配体-受体轴通讯在AD的发生和发展中发挥作用的观点。特别是，我们的分析确定了CXCR 4、EGFR、MAP 4K 4和IGF 1 R作为AD的潜在生物标志物和治疗靶点。
Alzheimer’s disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
2.1
作者：
Mantzavinos V;Alexiou A
通讯作者：
Alexiou A
p25 转基因小鼠神经祖细胞增殖的短暂增强及其长期存活的损害。
影响因子：
--
作者：
Zou D;Zhou Y;Liu L;Dong F;Shu T;Zhou Y;Tsai LH;Mao Y
通讯作者：
Mao Y
DOI：
10.1007/978-1-4939-7000-1_26
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Burley SK;Berman HM;Kleywegt GJ;Markley JL;Nakamura H;Velankar S
通讯作者：
Velankar S
DOI：
10.3233/jad-179939
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Bennett DA;Buchman AS;Boyle PA;Barnes LL;Wilson RS;Schneider JA
通讯作者：
Schneider JA