Shen Junlin, Yang Bingbing, Xie Zhonghua, Wu Heng, Zheng Zhanye, Wang Jianhua, Wang Ping, Zhang Peng, Li Wei, Ye Zhaoxiang, Yu Chunshui
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
Department of Mathematics, School of Science, Tianjin University of Science and Technology, Tianjin, China.
Front Neurosci. 2021 Apr 20;15:639527. doi: 10.3389/fnins.2021.639527. eCollection 2021.
Mapping gene expression profiles to neuroimaging phenotypes in the same anatomical space provides opportunities to discover molecular substrates for human brain functional properties. Here, we aimed to identify cell-type-specific gene modules associated with the regional homogeneity (ReHo) of spontaneous brain activity and their associations with brain disorders. Fourteen gene modules were consistently associated with ReHo in the three datasets, five of which showed cell-type-specific expression (one neuron-endothelial module, one neuron module, one astrocyte module and two microglial modules) in two independent cell series of the human cerebral cortex. The neuron-endothelial module was mainly enriched for transporter complexes, the neuron module for the synaptic membrane, the astrocyte module for amino acid metabolism, and microglial modules for leukocyte activation and ribose phosphate biosynthesis. In enrichment analyses of cell-type-specific modules for 10 common brain disorders, only the microglial module was significantly enriched for genes obtained from genome-wide association studies of multiple sclerosis (MS) and Alzheimer's disease (AD). The ReHo of spontaneous brain activity is associated with the gene expression profiles of neurons, astrocytes, microglia and endothelial cells. The microglia-related genes associated with MS and AD may provide possible molecular substrates for ReHo abnormality in both brain disorders.
将基因表达谱映射到相同解剖空间中的神经影像表型，为发现人类脑功能特性的分子基础提供了机会。在此，我们旨在识别与自发脑活动的局部一致性（ReHo）相关的细胞类型特异性基因模块及其与脑部疾病的关联。在三个数据集中，有14个基因模块始终与ReHo相关，其中5个在人类大脑皮层的两个独立细胞系列中表现出细胞类型特异性表达（一个神经元-内皮细胞模块、一个神经元模块、一个星形胶质细胞模块和两个小胶质细胞模块）。神经元-内皮细胞模块主要富集于转运蛋白复合物，神经元模块富集于突触膜，星形胶质细胞模块富集于氨基酸代谢，小胶质细胞模块富集于白细胞激活和磷酸核糖生物合成。在针对10种常见脑部疾病的细胞类型特异性模块的富集分析中，只有小胶质细胞模块在来自多发性硬化症（MS）和阿尔茨海默病（AD）全基因组关联研究的基因中显著富集。自发脑活动的ReHo与神经元、星形胶质细胞、小胶质细胞和内皮细胞的基因表达谱相关。与MS和AD相关的小胶质细胞相关基因可能为这两种脑部疾病中ReHo异常提供可能的分子基础。
