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Updated: Nov 10, 2025
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Transcriptome of microglia reveals a species-specific expression profile in bovines with conserved and new signature
Leticia Tavares-Gomes1,2, Camille Monney1, Géraldine Neuhaus1
1Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Abstract:
Evidence is growing that microglia adopt different roles than monocyte-derived macrophages (MDM) during CNS injury. However, knowledge about their function in the pathogenesis of neuroinfections is only rudimentary. Cattle are frequently affected by neuroinfections that are either zoonotic or related to diseases in humans, and, hence, studies of bovine neuroinfections as a natural disease model may generate fundamental data on their pathogenesis potentially translatable to humans. We investigated the transcriptomic landscape and lineage markers of bovine microglia and MDM. Although bovine microglia expressed most microglial signature genes known from humans and mice, they exhibited a species-specific transcriptomic profile, including strikingly low expression of TMEM119 and enrichment of the two scavenger receptors MEGF10 and LY75. P2RY12 was amongst the most enriched genes in bovine microglia, and antibodies against P2RY12 labeled specifically resting microglia, but also reactive microglia within neuroinfection foci in-situ. On the other hand, F13A1 was amongst the most enriched genes in bovine monocytes and MDM and, additionally, the encoded protein was expressed in-situ in monocytes and MDM in the inflamed brain but not in microglia, making it a promising marker for infiltrating MDM in the brain. In culture, primary bovine microglia downregulated signature genes, expressed markers of activation, and converged their transcriptome to MDM. However, they retained several microglia signature genes that clearly distinguished them from bovine MDM, making them a promising in-vitro tool to study mechanisms of microglia-pathogen interactions.
Insights
Bovine microglia and monocyte-derived macrophages (MDM) have distinct transcriptomic profiles. P2RY12 marks microglia, while F13A1 identifies infiltrating MDM in bovine neuroinfections, aiding disease research.
Area of Science:
- Neuroimmunology
- Comparative Pathology
- Transcriptomics
Background:
- Microglia and monocyte-derived macrophages (MDM) play different roles in CNS injury.
- Understanding their function in neuroinfections is crucial, especially in cattle, a natural model for human-relevant diseases.
Purpose of the Study:
- To investigate the transcriptomic landscape and lineage markers of bovine microglia and MDM.
- To identify species-specific markers for distinguishing these cell types in neuroinflammation.
Main Methods:
- Transcriptomic analysis of bovine microglia and MDM.
- In situ hybridization and immunohistochemistry using specific antibodies (P2RY12, F13A1).
- In vitro culture of primary bovine microglia.
Main Results:
- Bovine microglia share some human/mouse signature genes but have unique profiles (low TMEM119, high MEGF10, LY75, P2RY12).
- P2RY12 specifically labels resting and reactive microglia in situ.
- F13A1 is enriched in bovine monocytes and MDM, serving as a marker for infiltrating MDM in inflamed brains.
- Cultured microglia downregulate some signature genes but retain distinct markers differentiating them from MDM.
Conclusions:
- Bovine microglia and MDM exhibit distinct molecular signatures, with P2RY12 and F13A1 as valuable markers.
- These findings provide insights into bovine neuroinfections and offer potential translational data for human neuroinflammatory diseases.
- Primary bovine microglia cultures represent a useful in vitro model for studying microglia-pathogen interactions.
