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Cited by 571Neuroinflammation and Neurodegeneration MechanismsSingle-cell and spatial transcriptomicsNeurogenesis and neuroplasticity mechanisms

Microglial regional heterogeneity and its role in the brain

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Tan, Yun-Long, Yuan, Yi, Tian, Li·2020·Molecular Psychiatry
DOI 10.1038/s41380-019-0609-8PMC PMC6974435
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Abstract

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.

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  • It is well established that both astrocytes and microglia show regional heterogeneity at the transcriptome level.

    “A possible explanation for this phenomenon is that we analyzed the cortex and hippocampus together, while it is well established that both astrocytes and microglia show regional heterogeneity at the transcriptome level (Batiuk et al., 2020;Tan et al., 2020).”

    From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Tan et al., 2020

    The Introduction describes spatial patterns of astrocyte-specific genes, and “Heterogeneity in microglial molecular signature across CNS regions” reports transcriptomic studies showing regional differences in microglial gene expression. But that section also describes conflicting single-cell results, including adult mouse microglia with remarkably similar transcriptomes across regions. Thus the source supports regional transcriptomic heterogeneity in both cell types, but not the unqualified assertion that it is well established for microglia. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Microglia comprise 0.5-16.6% of the total cell population in the adult brain and spinal cord, depending on anatomical region, sex, and stage of development.

    “Microglia comprise 0.5–16.6% of the total cell population in the adult brain and spinal cord, depending on the anatomical region, sex, and stage of development, among other variables [307,308].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [308]

    The section “Heterogeneity in microglial density across CNS regions” reports regional differences in microglial abundance, including lower abundance in the cerebellum and spinal cord than in cortical regions, and describes heterogeneity in embryonic and adult brains. It does not give the claimed 0.5–16.6% share of total cells or establish sex as a determinant of that share. Its 0.5–2.5% figure refers instead to a proliferation rate. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Tan, Y.-L., Yuan, Y., & Tian, L.
Affiliations
  • Children's Hospital of Capital Institute of Pediatrics (CN)
  • Peking University (CN)
Corresponding author
Tian, Li
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2019-11-26
Volume
25
Issue
2
Pages
351-367
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-019-0609-8
PMC
PMC6974435
OpenAlex
W2990866005
Cited by
571
References
31
Citations by year
2026: 74 · 2025: 88 · 2024: 105 · 2023: 85 · 2022: 91 · 2021: 77 · 2020: 51
FWCI
5.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • European Commission
  • Eesti Teadusagentuur (MOBTT77)
  • Beijing Municipal Science and Technology Commission (Z171100001017021)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
microglia, regional heterogeneity, single-cell transcriptomics, bulk RNA-seq, central nervous system, neuron-glia interactions, neuropsychiatric disorders
MeSH terms
Animals, Brain, Central Nervous System, Central Nervous System Diseases, Humans, Neurons, Microglia, Transcriptome

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