Departments of Neurology and Radiology, Massachusetts General Hospital, NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA.
Department of Neurosurgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Int J Mol Sci. 2021 Feb 2;22(3):1495. doi: 10.3390/ijms22031495.
One of the essential functions of microglia is to continuously sense changes in their environment and adapt to those changes. For this purpose, they use a set of genes termed the sensome. This sensome is comprised of the most abundantly expressed receptors on the surface of microglia. In this study, we updated previously identified mouse microglial sensome by incorporating an additional published RNAseq dataset into the data-analysis pipeline. We also identified members of the human microglial sensome using two independent human microglia RNAseq data sources. Using both the mouse and human microglia sensomes, we identified a key set of genes conserved between the mouse and human microglial sensomes as well as some differences between the species. We found a key set of 57 genes to be conserved in both mouse and human microglial sensomes. We define these genes as the "microglia core sensome". We then analyzed expression of genes in this core sensome in five different datasets from two neurodegenerative disease models at various stages of the diseases and found that, overall, changes in the level of expression of microglial sensome genes are specific to the disease or condition studied. Our results highlight the relevance of data generated in mice for understanding the biology of human microglia, but also stress the importance of species-specific gene sets for the investigation of diseases involving microglia. Defining this microglial specific core sensome may help identify pathological changes in microglia in humans and mouse models of human disease.
小胶质细胞的基本功能之一是不断感知其环境的变化,并适应这些变化。为此,它们使用一组被称为传感组的基因。这个传感组由小胶质细胞表面表达最丰富的受体组成。在这项研究中,我们通过将另一个已发表的 RNAseq 数据集纳入数据分析管道,更新了先前鉴定的小鼠小胶质细胞传感组。我们还使用两个独立的人类小胶质细胞 RNAseq 数据源鉴定了人类小胶质细胞传感组的成员。使用小鼠和人类小胶质细胞传感组,我们鉴定出了一组在小鼠和人类小胶质细胞传感组之间保守的关键基因,以及物种之间的一些差异。我们发现有一组 57 个基因在小鼠和人类小胶质细胞传感组中都保守。我们将这些基因定义为“小胶质细胞核心传感组”。然后,我们分析了五个不同数据集中小胶质细胞核心传感组中基因的表达,这些数据集来自两种神经退行性疾病模型的不同疾病阶段,结果发现,总的来说,小胶质细胞传感组基因表达水平的变化是特定于所研究的疾病或状况的。我们的研究结果突出了在小鼠中生成的数据对于理解人类小胶质细胞生物学的相关性,但也强调了特定于物种的基因集对于研究涉及小胶质细胞的疾病的重要性。定义这个小胶质细胞特有的核心传感组可能有助于识别人类和人类疾病小鼠模型中小胶质细胞的病理变化。