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Published

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

Authors

Amy F Lloyd, Anna Martinez-Muriana, Emma Davis, Michael J D Daniels, Pengfei Hou, Renzo Mancuso, Alejandro J Brenes, Linda V Sinclair, Ivana Geric, An Snellinx, Katleen Craessaerts, Tom Theys, Mark Fiers, Bart De Strooper, Andrew J M Howden

Abstract

Cell Rep. 2024 Oct 25;43(11):114908. doi: 10.1016/j.celrep.2024.114908. Online ahead of print.

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.

PMID:39460937 | DOI:10.1016/j.celrep.2024.114908

UK DRI Authors

Bart De Strooper

Prof Bart De Strooper

Group Leader

Investigating the cellular reaction to amyloid beta and tau protein in Alzheimer's disease

Prof Bart De Strooper