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Updated: Jun 29, 2025
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
The proteomic landscape of microglia in health and disease
Emma Davis1,2, Amy F Lloyd3
1The Francis Crick Institute, London, United Kingdom.
Abstract:
Microglia are the resident immune cells of the central nervous system (CNS) and as such play crucial roles in regulating brain homeostasis. Their presence in neurodegenerative diseases is known, with neurodegeneration-associated risk genes heavily expressed in microglia, highlighting their importance in contributing to disease pathogenesis. Transcriptomics studies have uncovered the heterogeneous landscape of microglia in health and disease, identifying important disease-associated signatures such as DAM, and insight into both the regional and temporal diversity of microglia phenotypes. Quantitative mass spectrometry methods are ever increasing in the field of neurodegeneration, utilised as ways to identify disease biomarkers and to gain deeper understanding of disease pathology. Proteins are the main mechanistic indicators of cellular function, yet discordance between transcript and proteomic findings has highlighted the need for in-depth proteomic phenotypic and functional analysis to fully understand disease kinetics at the cellular and molecular level. This review details the current progress of using proteomics to define microglia biology, the relationship between gene and protein expression in microglia, and the future of proteomics and emerging methods aiming to resolve heterogeneous cell landscapes.
Insights
Microglia, the brain's immune cells, are vital in neurodegenerative diseases. Proteomics offers a deeper understanding of their function and the link between gene and protein expression in disease.
Area of Science:
- Neuroscience
- Immunology
- Proteomics
Background:
- Microglia are central nervous system (CNS) immune cells crucial for brain homeostasis.
- Their role in neurodegenerative diseases is significant, with risk genes highly expressed in microglia.
- Transcriptomics reveals microglia heterogeneity and disease-associated signatures like DAM.
Purpose of the Study:
- To review the application of proteomics in defining microglia biology.
- To explore the relationship between gene and protein expression in microglia.
- To discuss the future of proteomics in resolving heterogeneous microglia landscapes.
Main Methods:
- Quantitative mass spectrometry for biomarker identification and pathology understanding.
- Proteomic phenotypic and functional analysis to complement transcriptomic data.
- Review of current literature on microglia proteomics.
Main Results:
- Proteomics provides mechanistic insights into cellular function, complementing transcriptomics.
- Discordance between transcript and protein levels necessitates proteomic analysis.
- Proteomics aids in understanding disease kinetics at the cellular and molecular level.
Conclusions:
- Proteomics is essential for a comprehensive understanding of microglia in health and disease.
- Further proteomic studies are needed to resolve microglia heterogeneity.
- Emerging proteomic methods promise advanced insights into CNS immune cell function.
