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Nat Neurosci. 2019 Dec;22(12):2098-2110. doi: 10.1038/s41593-019-0532-y. Epub 2019 Nov 18.

Mapping microglia states in the human brain through the integration of high-dimensional techniques.

Author information

1
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
2
Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
3
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
5
AC Immune, Lausanne, Switzerland.
6
Department of Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
7
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany. gruen@ie-freiburg.mpg.de.
8
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg im Breisgau, Germany. gruen@ie-freiburg.mpg.de.
9
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. josef.priller@charite.de.
10
DZNE and BIH, Berlin, Germany. josef.priller@charite.de.
11
University of Edinburgh and UK DRI, Edinburgh, UK. josef.priller@charite.de.
12
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. marco.prinz@uniklinik-freiburg.de.
13
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg im Breisgau, Germany. marco.prinz@uniklinik-freiburg.de.
14
Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany. marco.prinz@uniklinik-freiburg.de.

Abstract

Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.

PMID:
31740814
DOI:
10.1038/s41593-019-0532-y

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