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

Chotima Böttcher, Stephan Schlickeiser, Marjolein A. M. Sneeboer, Desiree Kunkel, Anniki Knop, Evdokia Paza, Pawel Fidzinski, Larissa Kraus, Gijsje J. L. Snijders, René S Kahn, Axel R Schulz, Henrik E Mei, Elly M. Hol, Britta Siegmund, Rainer Glauben, Eike J Spruth, Lot D De Witte, Josef Priller

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)78-90
Number of pages13
JournalNature Neuroscience
Volume22
Issue number1
Early online date17 Dec 2018
DOIs
Publication statusPublished - 31 Jan 2019

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