| First Author | Pan M | Year | 2026 |
| Journal | Dev Cell | Volume | 61 |
| Issue | 7 | Pages | 1504-1520.e8 |
| PubMed ID | 42314681 | Mgi Jnum | J:388016 |
| Mgi Id | MGI:8354645 | Doi | 10.1016/j.devcel.2026.05.012 |
| Citation | Pan M, et al. (2026) Organoid modeling of lung branching morphogenesis and epithelial lineage specification. Dev Cell |
| abstractText | Branching morphogenesis is a fundamental process governing pulmonary development, epithelial differentiation, and functional maturation. Here, we report a multilevel branching lung organoid (BLO) model generated from primary tip epithelial cells using a robust, chemically defined protocol. These BLOs exhibit characteristic dendritic architectures with proximodistal patterning and alveolar-sac-like structures. Time-resolved single-cell RNA sequencing reveals that BLOs comprise both proximal airway and distal alveolar epithelial populations and recapitulate the developmental trajectories of lung epithelial lineages in vitro. Live-cell imaging further demonstrates that the spatial organization and branching dynamics of BLOs closely resemble those of native murine pulmonary epithelium in vivo. Upon transplantation into bleomycin-injured murine models, BLO-derived cells further mature and ameliorate pulmonary fibrosis. Together, these findings establish BLOs as a powerful platform for investigating lung branching morphogenesis, epithelial lineage specification and regeneration. |
