A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease
A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease
Summary 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 health. We report location-dependent airway epithelial cell states, and a novel subset of tissue-resident memory T cells. In lower airways of asthma patients, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report presence of pathogenic effector Th2 cells in asthma, and find evidence for type-2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identify a shift from airway structural cell communication in health to a Th2-dominated interactome in asthma.
Meyer K.B.、Vento-Tormo R.、Firth H.V.、Mahbubani K.T.A.、Cvejic A.、Saeb-Parsy K.、Vieira Braga F.A.、Kar G.、Berg M.、Brouwer S.、Gomes T.、Luinge M.、Timens W.、Angelidis I.、Strunz M.、Theis F.J.、Efremova M.、Affleck K.、Nawijn M.C.、Brandsma C.-A.、Koppelman G.H.、Polanski K.、Jiang J.、Schiller H.B.、Simon L.M.、Strzelecka P.、Fasouli E.S.、van Oosterhout A.J.、Teichmann S.A.、Carpaij O.A.、van den Berge M.、Hesse L.、Palit S.
Wellcome Sanger InstituteWellcome Sanger InstituteWellcome Sanger InstituteDepartment of Surgery, University of CambridgeWellcome Sanger Institute||Department of Haematology, University of Cambridge||Cambridge Stem Cell InstituteDepartment of Surgery, University of CambridgeWellcome Sanger Institute||Open TargetsWellcome Sanger Institute||Open TargetsUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenWellcome Sanger InstituteUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenHelmholtz Zentrum M¨1nchen, German Research Center for Environmental Health, Institute of Lung Biology and DiseaseHelmholtz Zentrum M¨1nchen, German Research Center for Environmental Health, Institute of Lung Biology and DiseaseHelmholtz Zentrum M¨1nchen, German Research Center for Environmental Health, Institute of Computational Biology||Department of Mathematics, Technische Universit?t M¨1nchenWellcome Sanger InstituteAllergic Inflammation Discovery Performance UnitUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenGroningen Research Institute for Asthma and COPD (GRIAC), University of Groningen||University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric AllergologyWellcome Sanger InstituteUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenHelmholtz Zentrum M¨1nchen, German Research Center for Environmental Health, Institute of Lung Biology and DiseaseHelmholtz Zentrum M¨1nchen, German Research Center for Environmental Health, Institute of Computational BiologyWellcome Sanger Institute||Department of Haematology, University of Cambridge||Cambridge Stem Cell InstituteWellcome Sanger Institute||Open TargetsAllergic Inflammation Discovery Performance UnitWellcome Sanger Institute||Open Targets||Theory of Condensed Matter Group, Cavendish Laboratory/Dept Physics, University of CambridgeGroningen Research Institute for Asthma and COPD (GRIAC), University of Groningen||University Medical Center Groningen, Department of PulmonologyGroningen Research Institute for Asthma and COPD (GRIAC), University of Groningen||University Medical Center Groningen, Department of PulmonologyUniversity of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology University of Groningen||Groningen Research Institute for Asthma and COPD (GRIAC), University of GroningenHelmholtz Zentrum M¨1nchen, German Research Center for Environmental Health, Institute of Computational Biology
基础医学细胞生物学分子生物学
Meyer K.B.,Vento-Tormo R.,Firth H.V.,Mahbubani K.T.A.,Cvejic A.,Saeb-Parsy K.,Vieira Braga F.A.,Kar G.,Berg M.,Brouwer S.,Gomes T.,Luinge M.,Timens W.,Angelidis I.,Strunz M.,Theis F.J.,Efremova M.,Affleck K.,Nawijn M.C.,Brandsma C.-A.,Koppelman G.H.,Polanski K.,Jiang J.,Schiller H.B.,Simon L.M.,Strzelecka P.,Fasouli E.S.,van Oosterhout A.J.,Teichmann S.A.,Carpaij O.A.,van den Berge M.,Hesse L.,Palit S..A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease[EB/OL].(2025-03-28)[2025-05-29].https://www.biorxiv.org/content/10.1101/527408.点此复制
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