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Nat Neurosci. 2019 Jan;22(1):78-90. doi: 10.1038/s41593-018-0290-2. Epub 2018 Dec 17.

Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry.

Author information

1
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. chotima.boettcher@charite.de.
2
Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.
3
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
5
Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
6
Berlin Institute of Health, Berlin, Germany.
7
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
8
German Rheumatism Research Center, Berlin, Germany.
9
Department of Neuroimmunology, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, Amsterdam, the Netherlands.
10
Medical Department for Gastroenterology, Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
11
DZNE, Berlin, Germany.
12
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. josef.priller@charite.de.
13
Berlin Institute of Health, Berlin, Germany. josef.priller@charite.de.
14
DZNE, Berlin, Germany. josef.priller@charite.de.
15
Cluster of Excellence NeuroCure, Berlin, Germany. josef.priller@charite.de.
16
University of Edinburgh and UK Dementia Research Institute, Edinburgh, UK. josef.priller@charite.de.

Abstract

Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (103 - 104 cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.

PMID:
30559476
DOI:
10.1038/s41593-018-0290-2

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