Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures

EMBO Rep. 2018 Nov;19(11):e46171. doi: 10.15252/embr.201846171. Epub 2018 Sep 11.


Microglia are specialized parenchymal-resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single-cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)-injected mice. By excluding the contribution of other immune CNS-resident and peripheral cells, we show that microglia isolated from LPS-injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease-associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.

Keywords: heterogeneity; lipopolysaccharide; microglia; neuroinflammation; single‐cell RNA‐seq.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / metabolism
  • Encephalitis / genetics
  • Encephalitis / metabolism
  • Encephalitis / pathology
  • Female
  • Flow Cytometry / methods
  • Gene Expression Regulation
  • Homeostasis
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Leukocyte Common Antigens / metabolism
  • Lipopolysaccharides / toxicity
  • Male
  • Mice, Inbred C57BL
  • Microglia / immunology
  • Microglia / metabolism*
  • Microglia / pathology
  • Neurodegenerative Diseases / pathology
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods*


  • CD11b Antigen
  • Lipopolysaccharides
  • Leukocyte Common Antigens
  • Ptprc protein, mouse