<i>Let-7</i> restrains an oncogenic circuit in AT2 cells to prevent fibrogenic cell intermediates in pulmonary fibrosis.

ABSTRACT: Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation. Using mice and organoid models, we demonstrate genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and results in accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integratio

SUBMITTER: Seasock MJ 

PROVIDER: S-EPMC11142151 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature