Progenitor potential of lung epithelial organoid cells in a transplantation model

• Published in: Cell reports (Cambridge) Vol. 39; no. 2; p. 110662
• Main Authors: Louie, Sharon M., Moye, Aaron L., Wong, Irene G., Lu, Emery, Shehaj, Andrea, Garcia-de-Alba, Carolina, Ararat, Erhan, Raby, Benjamin A., Lu, Bao, Paschini, Margherita, Bronson, Roderick T., Kim, Carla F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.04.2022
• Subjects: airway; alveolar; Animals; Cell Differentiation; Epithelial Cells; Lung; lung epithelial cells; lung progenitor cells; lung regeneration; lung stem cells; Mice; Organoids; single-cell RNA sequencing; Spinocerebellar Ataxias; Stem Cells; transplantation; single-cell RNA sequencing; CP: Stem cell research; organoids; airway; transplantation; alveolar; lung epithelial cells; lung progenitor cells; lung stem cells; lung regeneration
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110662

Lung progenitor cells are crucial for regeneration following injury, yet it is unclear whether lung progenitor cells can be functionally engrafted after transplantation. We transplanted organoid cells derived from alveolar type II (AT2) cells enriched by SCA1-negative status (SNO) or multipotent SCA1-positive progenitor cells (SPO) into injured mouse lungs. Transplanted SNO cells are retained in the alveolar regions, whereas SPO cells incorporate into airway and alveolar regions. Single-cell transcriptomics demonstrate that transplanted SNO cells are comparable to native AT2 cells. Transplanted SPO cells exhibit transcriptional hallmarks of alveolar and airway cells, as well as transitional cell states identified in disease. Transplanted cells proliferate after re-injury of recipient mice and retain organoid-forming capacity. Thus, lung epithelial organoid cells exhibit progenitor cell functions after reintroduction to the lung. This study reveals methods to interrogate lung progenitor cell potential and model transitional cell states relevant to pathogenic features of lung disease in vivo. [Display omitted] •Alveolar organoid cells engraft into the alveolar space•Transplanted lung alveolar cells have transcriptional signature of native AT2 cells•Transplanted alveolar cells proliferate and retain organoid-forming capacity•Organoid cells undergo changes to transitional cell states upon transplantation Upon return to the lung via transplantation, lung epithelial progenitor cells from organoid cultures restore their native transcriptional state and retain progenitor cell function. Louie et al. show future cell-based therapies, reveal methods to interrogate lung progenitor cell potential, and model transitional cell states relevant to lung disease in vivo.