biostudies-literatureUnknownWarren RNHLBI NIH HHSIdiopathic pulmonary fibrosis (IPF) is a progressive scarring disease arising from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than into alveolar type 1 (AT1) cells, which are responsible for gas exchange. Here, we report that healthy lungs maintain their stem cells through tonic Hippo and β-catenin signaling, which promote Yap/Taz degradation and allow for low level expression of the Wnt target gene <i>Myc</i>. Inactivation of upstream activators of the Hippo pathway in lung stem cells inhibits this tonic β-catenin signaling and <i>Myc</i> expression and promotes their Taz mediated differentiation into AT1 cells. Vice versa, increased Myc in collaboration with Yap promotes the differentiation of lung stem cells along the basal and myoepitheliaResearch squarers.3.rs-4177351https://www.ebi.ac.uk/biostudies/studies/S-EPMC11092845biostudies-literatureCell competition drives bronchiolization and pulmonary fibrosis.PMC11092845R01 HL132156T32 HL105355R01 HL146461R35 HL161169Stripp BWarren RKlinkhammer KLyu HDe Langhe SPYao CfalseCell competition drives bronchiolization and pulmonary fibrosis.Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease arising from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than into alveolar type 1 (AT1) cells, which are responsible for gas exchange. Here, we report that healthy lungs maintain their stem cells through tonic Hippo and β-catenin signaling, which promote Yap/Taz degradation and allow for low level expression of the Wnt target gene <i>Myc</i>. Inactivation of upstream activators of the Hippo pathway in lung stem cells inhibits this tonic β-catenin signaling and <i>Myc</i> expression and promotes their Taz mediated differentiation into AT1 cells. Vice versa, increased Myc in collaboration with Yap promotes the differentiation of lung stem cells along the basal and myoepithelia2024-01-01T00:00:00Z2024 Apr2026-07-02T03:11:38.059Z2026-07-02T03:08:58.801ZS-EPMC110928453874630910.21203/rs.3.rs-4177351/v1