Epithelial-mesenchymal cell competition coordinates fate transitions across tissue compartments during lung development and fibrosis.

ABSTRACT: The coordination between epithelial progenitors and their mesenchymal niche is critical for organogenesis and repair, yet the mechanisms governing their competitive interactions remain unclear. Here, we reveal a paradigm of tissue-scale fitness sensing in the lung, where mesenchymal Yap levels antagonize epithelial Yap levels to dictate epithelial stem cell fate. We show that reduced fitness in alveolar fibroblasts (AF1s) via Yap/Taz or Myc deletion leads to their apoptotic elimination and a collapse of the alveolar stem cell niche. This niche collapse triggers a pathological competitive response from the epithelium, which undergoes aberrant bronchiolization that phenocopies human pulmonary fibrosis. Mechanistically, we uncovered a molecular switch that controls mesenchymal fate. During de

SUBMITTER: Klinkhammer K 

PROVIDER: S-EPMC12685993 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature