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Nat Neurosci
Published

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

Authors

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

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:

UK DRI Authors

Paul Matthews

Prof Paul Matthews

Group Leader

Exploring neuronal vulnerability and genetic risk variants in Alzheimer’s progression

Prof Paul Matthews
Josef Priller

Prof Josef Priller

Group Leader

Defining and modulating myeloid cell function in neurodegenerative diseases

Prof Josef Priller