Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures

Carole Sousa, Anna Golebiewska, Suresh K. Poovathingal, Tony Kaoma, Yolanda Pires-Afonso, Silvia Martina, Djalil Coowar, Francisco Azuaje, Alexander Skupin, Rudi Balling, Knut Biber, Simone P. Niclou, Alessandro Michelucci*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

116 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere46171
JournalEMBO Reports
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2018

Keywords

  • heterogeneity
  • lipopolysaccharide
  • microglia
  • neuroinflammation
  • single-cell RNA-seq

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