A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.

ABSTRACT: Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo. Here, we describe the development of mature, expandable AT2 organoids derived from human fetal lungs which are phenotypically stable, can differentiate into AT1-like cells, and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH,

SUBMITTER: Lim K 

PROVIDER: S-EPMC11790967 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature