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Nat Neurosci. 2019 Jun;22(6):1021-1035. doi: 10.1038/s41593-019-0393-4. Epub 2019 May 6.

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

Author information

1
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
2
Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
3
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
4
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
5
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium.
6
Cancer Research Institute Ghent, Ghent, Belgium.
7
Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, Center of Intestinal Neuro-immune Interactions, KU Leuven, Leuven, Belgium.
8
VIB Flow Core, VIB Center for Inflammation Research, Ghent, Belgium.
9
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
10
Department of Neuroscience, Janssen Research & Development (a division of Janssen Pharmaceutica NV), Beerse, Belgium.
11
Molecular and Cellular Oncology Laboratory, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
12
Barriers in Inflammation lab, VIB Center for Inflammation Research, Ghent, Belgium.
13
Ghent Gut Inflammation Group, Ghent University, Ghent, Belgium.
14
Host-Microbiota Interaction lab, VIB Center for Inflammation Research, Ghent, Belgium.
15
Department of Rheumatology, University Hospital Ghent, Ghent, Belgium.
16
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
17
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium. kiavash.movahedi@vub.vib.be.
18
Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium. kiavash.movahedi@vub.vib.be.

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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PMID:
31061494
DOI:
10.1038/s41593-019-0393-4
[Indexed for MEDLINE]

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