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

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 suscep...

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Published in:Nature neuroscience 2019-01, Vol.22 (1), p.78-90
Main Authors: Böttcher, Chotima, Schlickeiser, Stephan, Sneeboer, Marjolein A M, Kunkel, Desiree, Knop, Anniki, Paza, Evdokia, Fidzinski, Pawel, Kraus, Larissa, Snijders, Gijsje J L, Kahn, René S, Schulz, Axel R, Mei, Henrik E, Hol, Elly M, Siegmund, Britta, Glauben, Rainer, Spruth, Eike J, de Witte, Lot D, Priller, Josef
Format: Article
Language:English
Subjects:
Brain
Brain - cytology
Brain - metabolism
Central nervous system
Composition
Criminal investigation
Cryopreservation
Cytometry
Data analysis
Data processing
Female
Health aspects
Heterogeneity
Humans
Identification and classification
Immune system
Immunophenotyping
Information management
Lectins, C-Type - metabolism
Male
Mannose Receptor
Mannose-Binding Lectins - metabolism
Microglia
Microglia - cytology
Microglia - metabolism
Multidimensional data
Multiplexing
Myeloid cells
Myeloid Cells - cytology
Myeloid Cells - metabolism
Online analytical processing
Phenotype
Phenotypes
Physiological aspects
Receptors, Cell Surface - metabolism
Workflow
Workflow software
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Summary: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 (10 - 10 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.
ISSN:1097-6256
1546-1726
DOI:10.1038/s41593-018-0290-2