Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
| Autor: | Thion, Morgane Sonia, Low, Donovan, Silvin, Aymeric, Chen, Jinmiao, Grisel, Pauline, Schulte-Schrepping, Jonas, Blecher, Ronnie, Ulas, Thomas, Squarzoni, Paola, Hoeffel, Guillaume, Coulpier, Fanny, Siopi, Eleni, David, Friederike Sophie, Scholz, Claus, Shihui, Foo, Lum, Josephine, Amoyo, Arlaine Anne, Larbi, Anis, Poidinger, Michael, Buttgereit, Anne, Lledo, Pierre-Marie, Greter, Melanie, Chan, Jerry Kok Yen, Amit, Ido, Beyer, Marc, Schultze, Joachim Ludwig, Schlitzer, Andreas, Pettersson, Sven, Ginhoux, Florent, Garel, Sonia |
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| Přispěvatelé: | Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Bonn = University of Bonn, Weizmann Institute of Science [Rehovot, Israël], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), National Cancer Centre Singapore, Universität Zürich [Zürich] = University of Zurich (UZH), KK Women's and Children's Hospital [Singapore], Karolinska Institute, This work was supported by grants from the LKC School of Medicine, SCELSE, MOE (Tier1 grant), NIMBLE grant NTU, NTU GUTME grant, Swedish Medical Council (VR to S.P.), the DFG (SFB704 to J.L.S., M.B., and T.U. and SCHL 2116/1-1 to A.S.), the Federal Ministry for Economic Affairs and Energy (BMWi Project FASTGENOMICS to J.L.S.), the European Union’s Horizon 2020 (733100-SYSCID to M.B., J.S.S., and J.L.S.), INSERM, CNRS, the ERC Consolidator (NImO 616080 to S.G.), and from the Merlion Program (to S.G and F.G.). M.B., A.S., and J.L.S. are members of the Excellence Cluster ImmunoSensation. F.G. and S.G. are EMBO YIP awardees., Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, Agency for science, technology and research [Singapore] (A*STAR), GenomiqueENS (Genomique ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, National Cancer Centre Singapore (NCCS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Nanyang Technological University [Singapour], Karolinska Institutet [Stockholm], European Project: 616080,EC:FP7:ERC,ERC-2013-CoG,NIMO(2014), DUMENIL, Anita, Neural and Immune Orchestrators of Forebrain Wiring - NIMO - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616080 - VALID, University of Bonn, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), THION, Morgane Sonia, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
prenatal [SDV.IMM] Life Sciences [q-bio]/Immunology [SDV]Life Sciences [q-bio] microbiology [Prenatal Exposure Delayed Effects] microbiome metabolism [Microglia] [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Article antibiotics neuroinflammation Mice Sex Factors embryology [Brain] Antibiotics Pregnancy [SDV.BDD] Life Sciences [q-bio]/Development Biology cytology [Microglia] sex Animals Germ-Free Life Humans ddc:610 [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity [SDV.BDD]Life Sciences [q-bio]/Development Biology ComputingMilieux_MISCELLANEOUS Cells Cultured CXCR4 cytology [Brain] Macrophages neurodevelopmental disorders Microbiota Brain Cell Differentiation Chromatin Assembly and Disassembly Mice Inbred C57BL metabolism [Brain] germ-free Prenatal Exposure Delayed Effects [SDV.IMM]Life Sciences [q-bio]/Immunology embryogenesis Female Microglia Transcriptome |
| Zdroj: | Cell Cell, 2018, 172 (3), pp.500-516.e16. ⟨10.1016/j.cell.2017.11.042⟩ Cell, Elsevier, 2018, 172 (3), pp.500-516.e16. ⟨10.1016/j.cell.2017.11.042⟩ Cell 172(3), 500-516.e16 (2018). doi:10.1016/j.cell.2017.11.042 |
| ISSN: | 0092-8674 1097-4172 |
| Popis: | Summary Microglia are embryonically seeded macrophages that contribute to brain development, homeostasis, and pathologies. It is thus essential to decipher how microglial properties are temporally regulated by intrinsic and extrinsic factors, such as sexual identity and the microbiome. Here, we found that microglia undergo differentiation phases, discernable by transcriptomic signatures and chromatin accessibility landscapes, which can diverge in adult males and females. Remarkably, the absence of microbiome in germ-free mice had a time and sexually dimorphic impact both prenatally and postnatally: microglia were more profoundly perturbed in male embryos and female adults. Antibiotic treatment of adult mice triggered sexually biased microglial responses revealing both acute and long-term effects of microbiota depletion. Finally, human fetal microglia exhibited significant overlap with the murine transcriptomic signature. Our study shows that microglia respond to environmental challenges in a sex- and time-dependent manner from prenatal stages, with major implications for our understanding of microglial contributions to health and disease. Graphical Abstract Highlights • Microglia undergo sequential phases of differentiation during development • The maternal microbiome influences microglial properties during prenatal stages • The absence of the microbiome has a sex- and time-specific impact on microglia • Microbiome depletions have acute and long-term effects on microglial properties Microglia respond to environmental challenges, such as signals from the gut microbiome, in a sex- and time-dependent manner. |
| Databáze: | OpenAIRE |
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