Deep proteomic analysis of microglia reveals fundamental biological differences between model systems
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
Affiliations
Amy F. Lloyd
Cell Signaling and Immunology, University of Dundee, Dundee, UK; Corresponding author
Anna Martinez-Muriana
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Emma Davis
The Francis Crick Institute, London, UK; UK Dementia Research Institute at UCL, University College London, London, UK
Michael J.D. Daniels
UK Dementia Research Institute at University of Edinburgh, Edinburgh, UK
Pengfei Hou
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Renzo Mancuso
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; MINDlab, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium
Alejandro J. Brenes
Cell Signaling and Immunology, University of Dundee, Dundee, UK; Centre for Gene Regulation and Expression, University of Dundee, Dundee, UK
Linda V. Sinclair
Cell Signaling and Immunology, University of Dundee, Dundee, UK
Ivana Geric
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
An Snellinx
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Katleen Craessaerts
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Tom Theys
Department of Neurosciences, Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven, Belgium
Mark Fiers
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Bart De Strooper
VIB Center for Brain & Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; The Francis Crick Institute, London, UK; UK Dementia Research Institute at UCL, University College London, London, UK; Corresponding author
Andrew J.M. Howden
Cell Signaling and Immunology, University of Dundee, Dundee, UK; Corresponding author
Summary: 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.
