Cited by 1,160Neuroinflammation and Neurodegeneration MechanismsSingle-cell and spatial transcriptomicsNeurogenesis and neuroplasticity mechanisms

A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

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Van Hove, Hannah, Martens, Liesbet, Scheyltjens, Isabelle, De Vlaminck, Karen, Pombo Antunes, Ana Rita, De Prijck, Sofie, Vandamme, Niels, De Schepper, Sebastiaan +12 more·2019·Nature Neuroscience

Abstract

While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in both the healthy and diseased brain.

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Crossref · 10.1038/s41593-019-0393-4

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Authors
Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., Aerts, J., Berx, G., Boeckxstaens, G. E., Vandenbroucke, R. E., Vereecke, L., Moechars, D., Guilliams, M., Van Ginderachter, J. A., Saeys, Y., & Movahedi, K.
Affiliations
  • Ghent University (BE)
  • Vrije Universiteit Brussel (BE)
  • Janssen (Belgium) (BE)
  • KU Leuven (BE)
  • Ghent University Hospital (BE)
Corresponding author
Movahedi, Kiavash
Venue
Nature Neuroscience
Published
2019-05-06
Volume
22
Issue
6
Pages
1021-1035
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2943220296
Cited by
1,160
References
68
Citations by year
2026: 128 · 2025: 158 · 2024: 188 · 2023: 155 · 2022: 154 · 2021: 156 · 2020: 88 · 2019: 31
FWCI
42.76
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
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
brain macrophages, border-associated macrophages, choroid plexus, dura mater, microglia, IRF8, macrophage ontogeny, postnatal brain development
MeSH terms
Interferon Regulatory Factor-8, Animals, Brain, Cell Differentiation, Female, Macrophages, Male, Mice, Inbred C57BL

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