Single-cell transcriptomics reveals distinct microglia signatures under inflammation

Microglia are specialized parenchymal-resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglia responses are believed to worsen CNS diseases, nevertheless their impact during the neuroinflammatory processes remains largely obscure. Here, using a combination of multicolor flow cytometry and single-cell RNA sequencing, we comprehensively profiled microglia in the brain of lipopolysaccharide (LPS)-injected mice. By excluding the contribution of other immune CNS-resident and peripheral cells, we showed that microglia isolated from LPS-injected mice displayed a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identified distinct microglia activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease-associated profiles. These results provide insights into microglia heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases. Comparison of sorted microglia (CD11b+CD45int cells) between peripherally LPS-injected mice and saline control mice at single-cell resolution. One sample saline control and one sample LPS 24h (from 2 mice per group; 1 female and 1 male)