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Design, infectability, and transcriptomic analysis of transregionally differentiated and scalable lung organoids derived from adult bronchial cells.
Valenzuela, Alicia Reyes; Turner, Mark; Markarian, Nathan; Lachance-Brais, Christophe; Hanrahan, John; Vali, Hojatollah; Vidal, Silvia; Mongeau, Luc.
Affiliation
  • Valenzuela AR; Biological and Biomedical Engineering, McGill University, Montreal, Quebec, Canada. H3A 2B4.
  • Turner M; Department of Mechanical engineering. McGill University. Montreal, Canada. H3A 0C3.
  • Markarian N; Pharmaceutical Drugs Directorate, Bureau of Gastroenterology, Infection and Viral Diseases, Health Canada, Ottawa, Ontario, Canada, K1A 0K9.
  • Lachance-Brais C; Department of Human Genetics, McGill University, Montreal, Canada, H3A 0C7.
  • Hanrahan J; Research Centre on Complex Traits, McGill University, Montreal, Canada, H3G 0B1.
  • Vali H; Swine and Poultry Infectious Diseases Research Center and Research Group on Infectious Diseases in Production Animals, Faculty of Veterinary Medicine, University of Montreal. Montreal, Canada, J25 2MD.
  • Vidal S; Chemistry Department, McGill University, Montreal, Quebec, Canada. H3A 0B8.
  • Mongeau L; Department of Physiology, McGill University, Montreal, Canada. H3G 1Y6.
bioRxiv ; 2024 Jul 09.
Article in En | MEDLINE | ID: mdl-39026877
ABSTRACT
The lung is a primary target for many lethal respiratory viruses, leading to significant global mortality. Current organoid models fail to completely mimic the cellular diversity and intricate tubular and branching structures of the human lung. Lung organoids derived from adult primary cells have so far only included cells from the input cell region, proximal or distal. Existing models are expensive. They often require cells from invasive deep lung tissue biopsies. The present study aimed to address these limitations. The lung organoids obtained using an original protocol exhibited transregional differentiation and were derived from relatively more accessible primary cells from the trachea/bronchi. Immortal bronchial cell lines were also used to simplify organoid fabrication and improve its scalability. The lung organoids are formed starting from bronchial cells with fibroblasts feeder cells in an alginate hydrogel coated with base membrane zone proteins. Characterizations were performed using bulk RNA sequencing and tandem mass tags. The resulting organoids express markers of different lung regions and mimic to some extent the tubular and branching morphology of the lung. The proteomic profile of organoid from primary cells and from cell lines was found to evolve towards that of mature lung tissue. Upregulated genes were mostly related to the respiratory system, tube development, and various aspects of respiratory viral infections. Infection with SARS-CoV-2 and influenza H1N1 was successful and did not require organoid disassembly. The organoids matured within 21 days and did not require complex or expensive culture methods. Transregionally differentiated lung organoid may find applications for the study of emerging or re-emerging viral infections and fostering the development of novel in-vitro therapeutic strategies.

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Document type: Article Country of publication: United States