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

Autor: Böttcher C; Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. chotima.boettcher@charite.de., Schlickeiser S; Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany., Sneeboer MAM; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Kunkel D; Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany., Knop A; Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany., Paza E; Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany., Fidzinski P; Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Kraus L; Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany., Snijders GJL; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Kahn RS; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Schulz AR; German Rheumatism Research Center, Berlin, Germany., Mei HE; German Rheumatism Research Center, Berlin, Germany., Hol EM; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Neuroimmunology, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, Amsterdam, the Netherlands., Siegmund B; Medical Department for Gastroenterology, Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Glauben R; Medical Department for Gastroenterology, Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Spruth EJ; Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.; DZNE, Berlin, Germany., de Witte LD; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Priller J; Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. josef.priller@charite.de.; Berlin Institute of Health, Berlin, Germany. josef.priller@charite.de.; DZNE, Berlin, Germany. josef.priller@charite.de.; Cluster of Excellence NeuroCure, Berlin, Germany. josef.priller@charite.de.; University of Edinburgh and UK Dementia Research Institute, Edinburgh, UK. josef.priller@charite.de.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2019 Jan; Vol. 22 (1), pp. 78-90. Date of Electronic Publication: 2018 Dec 17.
DOI: 10.1038/s41593-018-0290-2
Abstrakt: 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 3 - 10 4 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.
Databáze: MEDLINE
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