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Science. 2019 Jan 25;363(6425). pii: eaat7554. doi: 10.1126/science.aat7554.

Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation.

Author information

1
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
2
Faculty of Biology, University of Freiburg, Freiburg, Germany.
3
Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany.
4
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
5
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.
6
Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
7
Cluster of Excellence BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany.
8
BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany.
9
Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
10
CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Germany.
11
Institute of Computer Science, University of Freiburg, Freiburg, Germany.
12
Life Imaging Center, Center for Biological Systems Analysis, Albert-Ludwigs University, Freiburg, Germany.
13
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
14
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. marco.prinz@uniklinik-freiburg.de.
15
Centre for NeuroModulation, University of Freiburg, Germany.
#
Contributed equally

Abstract

The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain's innate immune system.

PMID:
30679343
DOI:
10.1126/science.aat7554
[Indexed for MEDLINE]

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