Deep proteomic analysis of microglia reveals fundamental biological differences between model systems

Amy Lloyd (Lead / Corresponding author), Anna Martinez-Muriana, Emma Davis, Michael JD Daniels, Pengfei Hou, Renzo Mancuso, Alejandro J Murillo, Linda V Sinclair, Ivana Geric, An Snellinx, Katleen Craessaerts, Tom Theys, Bart De Strooper (Lead / Corresponding author), Andy Howden (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
48 Downloads (Pure)

Abstract

Using high-resolution quantitative mass spectrometry, we present comprehensive human and mouse microglia proteomic datasets consisting of over 11,000 proteins across six microglia groups. Microglia share a core protein signature of over 5,600 proteins, yet fundamental differences are observed between species and culture conditions. Mouse microglia demonstrate proteome differences in inflammation- and Alzheimer's disease-associated proteins. We identify differences in the protein content of ex vivo and in vitro cells and significant proteome differences associated with protein synthesis, metabolism, microglia marker expression, and environmental sensors. Culturing microglia induces rapidly increased growth, protein content, and inflammatory protein expression. These changes are restored by engrafting in vitro cells into the brain, with xenografted human embryonic stem cell (hESC)-derived microglia closely resembling microglia from the human brain. These data provide an important resource for the field and highlight important considerations needed when using model systems to study human physiology and pathology of microglia.

Original languageEnglish
Article number114908
Number of pages22
JournalCell Reports
Volume43
Issue number11
Early online date25 Oct 2024
DOIs
Publication statusPublished - 26 Nov 2024

Keywords

  • Microglia
  • proteomics
  • mass spectrometry
  • neuroimmunology
  • CP: Neuroscience

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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