Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease
Open accessAbstract
Genome‐wide expression profiling technology has resulted in detailed transcriptome data for a wide range of tissues, conditions and diseases. In neuroscience, expression datasets were mostly generated using whole brain tissue samples, resulting in data from a mixture of cell types, including glial cells and neurons. Over the past few years, a rapidly increasing number of expression profiling studies using isolated microglial cell populations have been reported. In these studies, the microglia transcriptome was compared to other cell types, such as other brain cells and peripheral tissue macrophages, and related to aging and neurodegenerative conditions. A commonality found in many of these studies was that microglia possess distinct gene expression signatures. This repertoire of selectively‐expressed microglial genes highlight functions beyond immune responses, such as synaptic modulation and neurotrophic support, and open up avenues to explore as‐yet‐unexpected roles. These data provide improved understanding of disease pathology, and complement not only the aforementioned whole brain tissue transcriptome studies, but also genome‐ and epigenome‐wide association studies. In this review, insights obtained from isolated microglia transcriptome studies are presented, and compared to studies using other genome‐wide approaches. The relation of microglia to other tissue macrophages and glial cell populations, as well as the role of microglia in the aging brain and in neurodegenerative conditions, will be discussed. Many more of these types of studies are expected in the near future, hopefully leading to the identification of novel genes and targets for neurodegenerative conditions. GLIA 2016;64:197–213
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During normal CNS function, microglia have a resting or homeostatic transcriptome profile that reflects a surveilling activity.
“During normal CNS function, microglia have a “resting,” or homeostatic, transcriptome profile that reflects a surveilling activity (36–41) (Figure 1).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [36]
In models of neurodegeneration, microglia express both neurotoxic and neuroprotective factors, as well as genes involved in oxidative phosphorylation and lysosome, ribosome, and spliceosome factors involved in responses to misfolded proteins, stress, and neuronal death or injury.
“In models of neurodegeneration, microglia express both neurotoxic and neuroprotective factors; genes involved in oxidative phosphorylation; and lysosome, ribosome, and spliceosome factors involved in responses to misfolded proteins, stress, and neuronal death or injury (36, 42) (Figure 1).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [36]
This expression profile concurs with other studies of DAM.
“This expression profile concurs with other studies of DAM [10,37,78,124,194].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [194]
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“This expression profile concurs with other studies of DAM [10,37,78,124,194].”
ResultInflammation in CNS neurodegenerative diseases
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- Authors
- Wes, P. D., Holtman, I. R., Boddeke, E. W. G. M., Möller, T., & Eggen, B. J. L.
- Affiliations
- Lundbeck (United States) (US)
- University Medical Center Groningen (NL)
- Corresponding author
- Wes, Paul D.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2015-06-04
- Volume
- 64
- Issue
- 2
- Pages
- 197-213
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W1535668109
- Cited by
- 167
- References
- 132
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 25 · 2023: 8 · 2022: 18 · 2021: 22 · 2020: 16 · 2019: 19 · 2018: 9 · 2017: 23 · 2016: 12 · 2015: 3
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Glia (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- microglia, microglial transcriptome, gene expression signatures, tissue macrophages, glial cells, brain aging, neurodegenerative diseases, synaptic modulation, neurotrophic support, microglial heterogeneity
- MeSH terms
- Animals, Humans, Macrophages, Microglia, Neurodegenerative Diseases, Gene Expression Profiling, Genomics, Epigenesis, Genetic
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