دورية أكاديمية

A cellular census of human lungs identifies novel cell states in health and in asthma.

التفاصيل البيبلوغرافية
العنوان: A cellular census of human lungs identifies novel cell states in health and in asthma.
المؤلفون: Vieira Braga FA; Wellcome Sanger Institute, Cambridge, UK.; Open Targets, Cambridge, UK., Kar G; Wellcome Sanger Institute, Cambridge, UK.; Open Targets, Cambridge, UK., Berg M; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Carpaij OA; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Polanski K; Wellcome Sanger Institute, Cambridge, UK., Simon LM; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany., Brouwer S; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Gomes T; Wellcome Sanger Institute, Cambridge, UK., Hesse L; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Jiang J; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Fasouli ES; Wellcome Sanger Institute, Cambridge, UK.; Open Targets, Cambridge, UK., Efremova M; Wellcome Sanger Institute, Cambridge, UK., Vento-Tormo R; Wellcome Sanger Institute, Cambridge, UK., Talavera-López C; Wellcome Sanger Institute, Cambridge, UK., Jonker MR; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Affleck K; Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, GlaxoSmithKline, Stevenage, UK., Palit S; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.; TranslaTUM, Technische Universität München, Munich, Germany.; Institute of Virology, Technische Universität München, Munich, Germany.; German Center for Infection Research, Partner Site Munich, Munich, Germany., Strzelecka PM; Wellcome Sanger Institute, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK.; Cambridge Stem Cell Institute, Cambridge, UK., Firth HV; Wellcome Sanger Institute, Cambridge, UK., Mahbubani KT; Department of Surgery, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK., Cvejic A; Wellcome Sanger Institute, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK.; Cambridge Stem Cell Institute, Cambridge, UK., Meyer KB; Wellcome Sanger Institute, Cambridge, UK., Saeb-Parsy K; Department of Surgery, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK., Luinge M; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Brandsma CA; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Timens W; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Angelidis I; Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany., Strunz M; Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany., Koppelman GH; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Oosterhout AJ; Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, GlaxoSmithKline, Stevenage, UK., Schiller HB; Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany., Theis FJ; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.; Department of Mathematics, Technische Universität München, Garching, Germany., van den Berge M; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Nawijn MC; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. m.c.nawijn@umcg.nl.; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. m.c.nawijn@umcg.nl., Teichmann SA; Wellcome Sanger Institute, Cambridge, UK. st9@sanger.ac.uk.; Open Targets, Cambridge, UK. st9@sanger.ac.uk.; Theory of Condensed Matter Group, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK. st9@sanger.ac.uk.
المصدر: Nature medicine [Nat Med] 2019 Jul; Vol. 25 (7), pp. 1153-1163. Date of Electronic Publication: 2019 Jun 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
أسماء مطبوعة: Publication: New York Ny : Nature Publishing Company
Original Publication: New York, NY : Nature Pub. Co., [1995-
مواضيع طبية MeSH: Asthma/*pathology , Lung/*cytology, Adult ; Aged ; CD4-Positive T-Lymphocytes/physiology ; Cell Communication ; Epithelial Cells/immunology ; Epithelial Cells/physiology ; Female ; Genome-Wide Association Study ; Goblet Cells/metabolism ; Humans ; Lung/immunology ; Lung/pathology ; Male ; Metaplasia ; Middle Aged ; Th2 Cells/physiology ; Transcriptome
مستخلص: Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (T H 2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identifies a shift from airway structural cell communication in healthy lungs to a T H 2-dominated interactome in asthmatic lungs.
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معلومات مُعتمدة: MC_PC_12009 United Kingdom MRC_ Medical Research Council
تواريخ الأحداث: Date Created: 20190619 Date Completed: 20191114 Latest Revision: 20210512
رمز التحديث: 20221213
DOI: 10.1038/s41591-019-0468-5
PMID: 31209336
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-170X
DOI:10.1038/s41591-019-0468-5