An overview of microglia ontogeny and maturation in the homeostatic and pathological brain

• Published in: The European journal of neuroscience Vol. 53; no. 11; pp. 3525 - 3547
• Main Authors: Mendes, Monique S., Majewska, Ania K., Dowd, Eilis
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01-06-2021
• Subjects: Brain; Central Nervous System; depletion; development; heterogeneity; Homeostasis; Life span; Maturation; microbiota; Microglia; Ontogeny; Phenotype; Phenotypes; repopulation; Transcription; depletion; microbiota; repopulation; development; microglia; heterogeneity
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15225

Microglia are the resident immune cells of the central nervous system (CNS) and are increasingly recognized as critical players in development, brain homeostasis, and disease pathogenesis. The lifespan, maintenance, proliferation, and turnover of microglia are important factors that regulate microglial behavior and affect their roles in the CNS. However, emerging evidence suggests that microglia are morphologically and phenotypically distinct in different brain areas, at different ages, and during disease. Ongoing research focuses on understanding how microglia acquire specific phenotypes in response to extrinsic cues in the environment and how phenotypes are specified by intrinsic properties of different populations of microglia. With the development of pharmacological and genetic tools that allow the investigation of microglia in vivo, there have been considerable advances in understanding molecular signatures of both homeostatic microglia and those reacting to injury and disease. Here, we review the master gene regulators that define microglia as well as discuss the evidence that microglia are heterogeneous and fall into distinct clusters that display specific intrinsic properties and perform unique tasks in different settings. Taken together, the information presented supports the idea that microglia morphology and transcriptional heterogeneity should be considered when studying the complex nature of microglia and their roles in brain health and disease.
Microglia are the resident macrophages of the brain and play critical roles in both health and disease. Microglia are morphologically and phenotypically distinct at different stages of life and in different regions of the brain. Here, we describe the diversity of microglial phenotypes and roles throughout development, adulthood, aging and disease using Alzheimer's disease as an example.