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Updated: Mar 24, 2026
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Microglial Physiology and Pathophysiology: Insights from Genome-wide Transcriptional Profiling
Andrea Crotti1, Richard M Ransohoff1
1Neuroimmunology, Biogen, 225 Binney Street, Cambridge, MA, 02142, USA.
Abstract:
Microglia originate from erythromyeloid progenitors (EMPs) in the yolk sac and develop in the forming CNS. Microglia are fundamental for the development and function of a healthy brain. By contrast, their role in immune host defense of the CNS remains speculative, given the immune privilege of this organ. Alterations in microglia functionality are involved in brain aging, as well as in neurodegenerative disease severity and progression. The combination of their ontogeny with the influence of the complex environment of the CNS makes microglia a unique cell population. Recent observations about microglia ontogeny combined with extensive gene expression profiling allow us to better capture the variety of nuances that microglia can manifest. Here, we provide a contemporary appraisal of microglial uniqueness based on their origin, functions, and expression profiles. Furthermore, we give an overview of the impact of aging and neurodegenerative diseases on microglia transcriptomes.
Insights
Microglia, crucial brain immune cells originating from yolk sac progenitors, are vital for brain development and function. Their unique characteristics and altered functions in aging and neurodegeneration are explored.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS).
- They originate from erythromyeloid progenitors (EMPs) in the yolk sac and develop within the CNS.
- Microglial function is critical for brain development and health, but their role in CNS immune defense is less understood due to the brain's immune privilege.
Purpose of the Study:
- To provide a contemporary appraisal of microglial uniqueness.
- To examine the influence of ontogeny and the CNS environment on microglia.
- To review the impact of aging and neurodegenerative diseases on microglia.
Main Methods:
- Analysis of recent observations on microglial ontogeny.
- Extensive gene expression profiling of microglia.
- Literature review on microglial functions and transcriptomes in aging and disease.
Main Results:
- Microglia possess unique characteristics stemming from their origin and CNS environment.
- Gene expression profiling reveals diverse microglial phenotypes.
- Aging and neurodegenerative diseases significantly alter microglial transcriptomes.
Conclusions:
- Microglia are a unique cell population with multifaceted roles in the CNS.
- Understanding microglial ontogeny and environmental interactions is key to their function.
- Alterations in microglia are implicated in brain aging and neurodegenerative diseases.
