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Long‐term expanding human airway organoids for disease modeling
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Abstract
Abstract Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.
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“Infection of murine gastric organoids by H. pylori showed increased cytosolic β-catenin levels induced by bacterially originated CagA, which led to increased proliferation in infected organoids179.”
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Metadata
- Authors
- Sachs, N., Papaspyropoulos, A., Zomer‐van Ommen, D. D., Heo, I., Böttinger, L., Klay, D., Weeber, F., Huelsz‐Prince, G., Iakobachvili, N., Amatngalim, G. D., de Ligt, J., van Hoeck, A., Proost, N., Viveen, M. C., Lyubimova, A., Teeven, L., Derakhshan, S., Korving, J., Begthel, H., Dekkers, J. F., Kumawat, K., Ramos, E., van Oosterhout, M. F., Offerhaus, G. J., Wiener, D. J., Olimpio, E. P., Dijkstra, K. K., Smit, E. F., van der Linden, M., Jaksani, S., van de Ven, M., Jonkers, J., Rios, A. C., Voest, E. E., van Moorsel, C. H., van der Ent, C. K., Cuppen, E., van Oudenaarden, A., Coenjaerts, F. E., Meyaard, L., Bont, L. J., Peters, P. J., Tans, S. J., van Zon, J. S., Boj, S. F., Vries, R. G., Beekman, J. M., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- St. Antonius Ziekenhuis (NL)
- The Netherlands Cancer Institute (NL)
- Institute for Atomic and Molecular Physics (NL)
- Maastricht University (NL)
- Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
- Princess Máxima Center (NL)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Corresponding author
- Clevers, Hans
- ORCID
- Sachs, Norman
- Papaspyropoulos, Angelos
- Klay, Dymph
- Weeber, Fleur
- Iakobachvili, Nino
- Amatngalim, Gimano D
- de Ligt, Joep
- van Hoeck, Arne
- Proost, Natalie
- Begthel, Harry
- Ramos, Emilio
- Offerhaus, G Johan
- Wiener, Dominique J
- Dijkstra, Krijn K
- Smit, Egbert F
- Jonkers, Jos
- Rios, Anne C
- Voest, Emile E
- Cuppen, Edwin
- Coenjaerts, Frank E
- Meyaard, Linde
- Bont, Louis J
- Peters, Peter J
- Tans, Sander J
- Boj, Sylvia F
- Vries, Robert G
- Beekman, Jeffrey M
- Clevers, Hans
- Venue
- The EMBO Journal
- Published
- 2019-01-14
- Volume
- 38
- Issue
- 4
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC6376275
- OpenAlex
- W2799736418
- Cited by
- 1,082
- References
- 82
- Citations by year
- 2026: 126 · 2025: 178 · 2024: 137 · 2023: 159 · 2022: 157 · 2021: 182 · 2020: 104 · 2019: 30
- FWCI
- 86.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by-nc-nd)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- AMOLF Institutional Repository (AMOLF) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, cc-by-nc-nd)
- Utrecht University Repository (Utrecht University) (submittedVersion, cc-by-nc-nd)
- Funders
- ZonMw (114021012, 40‐00812‐98‐14103, 91615182)
- Human Frontier Science Program (CDA00076/2014‐C)
- Prof. Dr. Jaap Swieringa Foundation (stAH‐CvM‐HI‐HC)
- Dutch Cystic Fibrosis Society (HIT‐CF)
- SU2C (SU2C‐AACR‐DT‐12‐14)
- KWF Kankerbestrijding (2014‐7006)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (680‐47‐529, 834.11.002)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- airway organoids, cystic fibrosis, CFTR function, lung cancer, metastasis, respiratory syncytial virus, NS2 protein, neutrophil recruitment, disease modeling, Clara cells, ciliated cells
- MeSH terms
- Animals, Carcinoma, Non-Small-Cell Lung, Cells, Cultured, Cystic Fibrosis, Disease Models, Animal, Drug Screening Assays, Antitumor, Epithelial Cells, Female, Humans, Lung Neoplasms, Male, Organ Culture Techniques, Organoids, Respiratory Syncytial Viruses, Respiratory System, Mice, SCID, Mice, Inbred NOD, Respiratory Syncytial Virus Infections, Cystic Fibrosis Transmembrane Conductance Regulator, Xenograft Model Antitumor Assays, Mice
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