Deep proteomic analysis of microglia reveals fundamental biological differences between model systems
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.
Authors
- Ivana Geric (ORCID: https://orcid.org/0000-0002-6184-0594)
- Bart De Strooper (ORCID: https://orcid.org/0000-0001-5455-5819)
- Tom Theys (ORCID: https://orcid.org/0000-0001-7595-3234)
- Renzo Mancuso (ORCID: https://orcid.org/0000-0002-7046-3348)
- Mark Fiers (ORCID: https://orcid.org/0000-0001-5694-2409)
- Alejandro J. Brenes (ORCID: https://orcid.org/0000-0001-8298-2463)
- Andrew J.M. Howden (ORCID: https://orcid.org/0000-0002-4332-9469)
- Amy Lloyd (ORCID: https://orcid.org/0000-0002-1168-5370)
- Emma Davis (ORCID: https://orcid.org/0000-0001-5820-6333)
- Anna Martínez‐Muriana (ORCID: https://orcid.org/0000-0002-8645-1317)
- Katleen Craessaerts (ORCID: https://orcid.org/0000-0001-6684-8475)
- Linda V. Sinclair (ORCID: https://orcid.org/0000-0003-1248-7189)
- Pengfei Hou (ORCID: https://orcid.org/0009-0009-6478-1364)
- Michael J. Daniels (ORCID: https://orcid.org/0000-0001-7489-5626)
- An Snellinx
Institutions
- Allen Institute for Brain Science (US)
- University of Dundee (GB)
- The Francis Crick Institute (GB)
- UK Dementia Research Institute (GB)
- VIB-UAntwerp Center for Molecular Neurology (BE)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- University College London (GB)
- University of Edinburgh (GB)
- KU Leuven (BE)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1016/j.celrep.2024.114908
- Citations
- 27
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 6.68
Funders
- Alzheimer's Society
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Onderzoeksraad, KU Leuven
- UK Dementia Research Institute
- Medical Research Council
- H2020 European Research Council