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Updated: Aug 2, 2025
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Microglia at the scene of the crime: what their transcriptomics reveal about brain health
Artem Arutyunov1,2, Robyn S Klein1,2,3,4
1Center for Neuroimmunology & Neuroinfectious Diseases.
Purpose Of Review:
Microglia, which arise from primitive myeloid precursors that enter the central nervous system (CNS) during early development, are the first responders to any perturbance of homeostasis. Although their activation has become synonymous with neurologic disease, it remains unclear whether microglial responses are the cause of or response to neuropathology. Here, we review new insights in the roles of microglia during CNS health and disease, including preclinical studies that transcriptionally profile microglia to define their functional states.
Recent Findings:
Converging evidence suggests that innate immune activation of microglia is associated with overlapping alterations in their gene expression profiles regardless of the trigger. Thus, recent studies examining neuroprotective microglial responses during infections and aging mirror those observed during chronic neurologic diseases, including neurodegeneration and stroke. Many of these insights derive from studies of microglial transcriptomes and function in preclinical models, some of which have been validated in human samples. During immune activation, microglia dismantle their homeostatic functions and transition into subsets capable of antigen presentation, phagocytosis of debris, and management of lipid homeostasis. These subsets can be identified during both normal and aberrant microglial responses, the latter of which may persist long-term. The loss of neuroprotective microglia, which maintain a variety of essential CNS functions, may therefore, in part, underlie the development of neurodegenerative diseases.
Summary:
Microglia exhibit a high level of plasticity, transforming into numerous subsets as they respond to innate immune triggers. Chronic loss of microglial homeostatic functions may underlie the development of diseases with pathological forgetting.
Insights
Microglia, the brain's immune cells, change function in response to injury. Their loss of protective roles may contribute to neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS).
- Microglial activation is linked to neurological diseases, but their precise role (cause or effect) is debated.
- Understanding microglial plasticity is crucial for CNS health and disease.
Approach:
- Review of recent preclinical studies and transcriptional profiling of microglia.
- Analysis of microglial functional states during various CNS conditions.
- Validation of findings in human samples where possible.
Key Points:
- Microglial gene expression profiles show conserved changes upon innate immune activation, irrespective of the trigger.
- Activated microglia shift from homeostatic functions to roles in antigen presentation, debris clearance, and lipid metabolism.
- Neuroprotective microglial functions are essential for CNS homeostasis; their chronic loss may drive neurodegeneration.
Conclusions:
- Microglia possess significant plasticity, adapting to diverse immune stimuli.
- Persistent loss of homeostatic microglial functions can contribute to the pathogenesis of neurodegenerative conditions, including those associated with cognitive decline.
