Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry
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; NBB-Psy
(2019) Nature Neuroscience, volume 22, issue 1, pp. 78 - 90
(Article)
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.
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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.
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Keywords: General Neuroscience
ISSN: 1097-6256
Publisher: Nature Publishing Group
Note: Funding Information: We thank C. Böttcher for excellent technical assistance with FACS analysis. We also acknowledge the assistance of the BCRT Flow Cytometry Lab (Charité – Universitätsmedizin Berlin, Germany). C.B. and J.P. were supported by the German Research Foundation (SFB TRR167, B05 & B07). J.P. received additional funding from the Berlin Institute of Health (CRG2aSP6) and the UK DRI (Momentum Award). S.S. was partially funded by the EU-H2020 project PACE (grant agreement number 733006). A.K. and E.P. were supported by stipends from the NeuroMac School (SFB TRR167, IRTG). A.K. received additional funding from the Cluster of Excellence NeuroCure. H.E.M. and A.R.S. were supported through grant Me3644/5-1. B.S. was supported by the German Research Foundation (SI 749/9-1, 749/10-1, CRC-TRR 241). B.S. and R.G. were supported by the Deutsche Krebhilfe (70112011). M.A.M.S. was supported by a 2014 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation and L.D.D.W. by the Virgo Consortium, funded by the Dutch government, project number FES0908. The psychiatric donor program of the Netherlands Brain Bank (NBB-Psy) is financially supported by the Netherlands Organization for Scientific Research (NWO). We acknowledge the Leibniz Science Campus for Chronic Inflammation for general support. Publisher Copyright: © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
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