Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures.

November 01, 2018 By:
  • Sousa C
  • Golebiewska A
  • Poovathingal SK
  • Kaoma T
  • Pires-Afonso Y
  • Martina S
  • Coowar D
  • Azuaje F
  • Skupin A
  • Balling R
  • Biber K
  • Niclou SP
  • Michelucci A.

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.

2018 Nov. EMBO Rep.19(11). Epub 2018 Sep 11.
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