Year: 2023
Type: article
Study design: Observational Study
Abstract: The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.
Source: Nature Medicine
Authors: Roman Sankowski, Patrick Süß, Alexander Benkendorff, Chotima Böttcher, Camila Fernandez-Zapata, Chintan Chhatbar, Jonathan Cahueau, Gianni Monaco, Adrià Dalmau Gasull, Ashkan Khavaran, Jürgen Grauvogel, Christian Scheiwe, Mukesch Johannes Shah, Dieter Henrik Heiland, Oliver Schnell, Filiz Markfeld-Erol, Mirjam Kunze, Robert Zeiser, Josef Priller, Marco Prinz
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Funders: Wellcome Trust, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Albert-Ludwigs-Universität Freiburg, Fritz Thyssen Stiftung, Gottfried Wilhelm Leibniz Universität Hannover, Novo Nordisk, Roman, Marga und Mareille Sobek Stiftung, National Institutes of Health, Medical Research Council, Leibniz-Gemeinschaft, Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg, HORIZON EUROPE European Research Council
Awards: G1014860659, G1078610655, G1284162446, IMMediate - Förderung von Advanced Clinician Scientists im Bereich immunvermittelter Erkrankungen, G181390637, G1844838350, G259924242, G2837854789, Zellsortiersystem, G2899880, G3256625789, G3523822304, G3544412130, SFB 1479: Onkogengetriebener Immun Escape (OncoEscape), G3986097662, TRR 359: Perinatale Entwicklung der ImmunzellTopologie (PILOT), G4866485077, EXC 2189: CIBSS Centre for Integrative Biological Signalling Studies, SFB 992: Medizinische Epigenetik (MEDEP) Von grundlegenden Mechanismen zu klinischen Anwendungen, G5188208403, TRR 167: Entwicklung, Funktion und Potential von myeloiden Zellen im zentralen Nervensystem (NeuroMac), KFO 5024: ImmunCheckpoints der Kommunikation zwischen Darm und Gehirn bei entzündlichen und neurodegenerativen Erkrankungen (GB.com), GRK 2162: Entwicklung und Vulnerabilität des Zentralnervensystems, G5931083012, G5976804734, G6000535164, Deciphering cellular signalling to cure graft-versus-host disease (GVHD) and leukemia relapse, G6952166915, G707554195, G7399536025, G7833425038
OpenAlex ID: W4390032293