1. A cellular census of human lungs identifies novel cell states in health and in asthma
- Author
-
Fabian J. Theis, Maarten van den Berge, Marnix R. Jonker, Paulina M. Strzelecka, Ana Cvejic, Roser Vento-Tormo, Mirjana Efremova, Karen Affleck, Felipe A. Vieira Braga, Sarah A. Teichmann, Carlos Talavera-López, Herbert B. Schiller, Sharon Brouwer, Eirini S. Fasouli, Marijn Berg, Laura Hesse, Antoon J. M. van Oosterhout, Corry-Anke Brandsma, Gerard H. Koppelman, Lukas M. Simon, Helen V. Firth, Krzysztof Polanski, Kourosh Saeb-Parsy, Tomás Gomes, Subarna Palit, Kerstin B. Meyer, Ilias Angelidis, Marjan Luinge, Gozde Kar, Martijn C. Nawijn, Orestes A Carpaij, Wim Timens, Maximilian Strunz, Jian Jiang, Krishnaa T. Mahbubani, Vieira Braga, Felipe A [0000-0003-0206-9258], Simon, Lukas M [0000-0001-6148-8861], Mahbubani, Krishnaa T [0000-0002-1327-2334], Meyer, Kerstin B [0000-0001-5906-1498], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Timens, Wim [0000-0002-4146-6363], Theis, Fabian J [0000-0002-2419-1943], Nawijn, Martijn C [0000-0003-3372-6521], Teichmann, Sarah A [0000-0002-6294-6366], Apollo - University of Cambridge Repository, Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Pharmaceutical and Pharmacological Sciences, Center of Experimental and Molecular Medicine, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,Cell ,PATHOGENESIS ,Cell Communication ,PHENOTYPE ,DISEASE ,0302 clinical medicine ,CD4-Positive T-Lymphocytes/physiology ,Medicine ,RNA-SEQ ,Th2 Cells/physiology ,MACROPHAGES ,Lung ,EPITHELIAL-CELLS ,General Medicine ,Hyperplasia ,respiratory system ,Middle Aged ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Goblet Cells ,medicine.symptom ,Asthma/pathology ,EXPRESSION ,Adult ,Cell signaling ,PROSTAGLANDIN D-2 ,Inflammation ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,Th2 Cells ,INFLAMMATION ,Lung/cytology ,Parenchyma ,Humans ,Aged ,Metaplasia ,business.industry ,Goblet Cells/metabolism ,Epithelial Cells/immunology ,Epithelial Cells ,medicine.disease ,GENE ,Epithelium ,Asthma ,respiratory tract diseases ,030104 developmental biology ,Immunology ,business ,Transcriptome ,Genome-Wide Association Study - Abstract
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 (TH2) 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 TH2-dominated interactome in asthmatic lungs.
- Published
- 2019