Microglial regional heterogeneity and its role in the brain

• Published in: Molecular psychiatry Vol. 25; no. 2; pp. 351 - 367
• Main Authors: Tan, Yun-Long, Yuan, Yi, Tian, Li
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2020; Nature Publishing Group
• Subjects: 631/378; 692/699/476; Animals; Behavioral Sciences; Biological Psychology; Brain - metabolism; Brain - physiology; Brain research; Cell number; Central nervous system; Central Nervous System - metabolism; Central Nervous System - physiology; Central Nervous System Diseases - pathology; Development and progression; Gene expression; Humans; Medicine; Medicine & Public Health; Mental disorders; Microglia; Microglia - metabolism; Microglia - physiology; Nervous system; Nervous system diseases; Neuronal-glial interactions; Neurons; Neurosciences; Pharmacotherapy; Physiology; Psychiatry; Review; Review Article; RNA sequencing; Spatial heterogeneity; Transcriptome; Transcriptomics; Canada
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-019-0609-8

Microglia have been recently shown to manifest a very interesting phenotypical heterogeneity across different regions in the mammalian central nervous system (CNS). However, the underlying mechanism and functional meaning of this phenomenon are currently unclear. Baseline diversities of adult microglia in their cell number, cellular and subcellular structures, molecular signature as well as relevant functions have been discovered. But recent transcriptomic studies using bulk RNAseq and single-cell RNAseq have produced conflicting results on region-specific signatures of microglia. It is highly speculative whether such spatial heterogeneity contributes to varying sensitivities of individual microglia to the same physiological and pathological signals in different CNS regions, and hence underlie their functional relevance for CNS disease development. This review aims to thoroughly summarize up-to-date knowledge on this specific topic and provide some insights on the potential underlying mechanisms, starting from microgliogenesis. Understanding regional heterogeneity of microglia in the context of their diverse neighboring neurons and other glia may provide an important clue for future development of innovative therapies for neuropsychiatric disorders.