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Updated: Aug 28, 2025
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with
Barbara B Shih1, Sarah M Brown1, Jack Barrington2,3
1The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
Abstract:
Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare. As a basis for improved understanding to enhance biomedical and agricultural research, we sought to characterize pig microglial identity at genome-wide scale and conduct inter-species comparisons. We isolated pig hippocampal tissue and microglia from frontal cortex, hippocampus, and cerebellum, as well as alveolar macrophages from the lungs and conducted RNA-sequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 239 highly enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 150 genes showing significant (adjusted p < 0.01) regional variations and that cerebellar microglia were most distinct. We compared normalized gene expression for microglia from human, mice and pigs using microglia signature gene lists derived from each species and demonstrated that a core microglial marker gene signature is conserved across species, but that species-specific expression subsets also exist. Our data provide a valuable resource defining the pig microglial transcriptome signature that validates and highlights pigs as a useful large animal species bridging between rodents and humans in which to study the role of microglia during homeostasis and disease.
Insights
Researchers characterized pig microglia, identifying a core gene signature conserved across species. This finding validates pigs as a valuable model for studying neurological disorders and animal welfare.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Microglia are crucial for brain health and disease, and understanding their function in pigs is vital for both biomedical research and animal welfare.
- Pigs serve as a relevant model for human neurological disorders linked to microglial dysfunction.
Purpose of the Study:
- To define the genome-wide transcriptomic signature of pig microglia.
- To compare pig microglia profiles with other species (human, mouse) and identify conserved and species-specific features.
- To establish pigs as a valuable large animal model for microglial research.
Main Methods:
- RNA sequencing (RNAseq) of pig microglia from frontal cortex, hippocampus, and cerebellum, alongside alveolar macrophages.
- Comparative transcriptomic analysis to identify a core porcine microglial gene signature.
- Cross-species comparison of microglial gene expression profiles.
Main Results:
- A set of 239 highly enriched genes defining the porcine core microglial signature was identified.
- Significant regional heterogeneity in pig microglia gene expression was observed, with cerebellar microglia being the most distinct.
- A conserved core microglial marker gene signature exists across humans, mice, and pigs, alongside species-specific expression patterns.
Conclusions:
- The study provides a comprehensive definition of the pig microglial transcriptome.
- Pig microglia share conserved core signatures with other species, supporting their utility as a large animal model.
- This research enhances understanding of microglia in homeostasis and disease, benefiting both biomedical and agricultural applications.
