Opposing roles for TGFβ- and BMP-signaling during nascent alveolar differentiation in the developing human lung.

ABSTRACT: Alveolar type 2 (AT2) cells function as stem cells in the adult lung and aid in repair after injury. The current study aimed to understand the signaling events that control differentiation of this therapeutically relevant cell type during human development. Using lung explant and organoid models, we identified opposing effects of TGFβ- and BMP-signaling, where inhibition of TGFβ- and activation of BMP-signaling in the context of high WNT- and FGF-signaling efficiently differentiated early lung progenitors into AT2-like cells in vitro. AT2-like cells differentiated in this manner exhibit surfactant processing and secretion capabilities, and long-term commitment to a mature AT2 phenotype when expanded in media optimized for primary AT2 culture. Comparing AT2-like cells differentiated with TG

SUBMITTER: Frum T 

PROVIDER: S-EPMC10492838 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature