
Idiopathic pulmonary fibrosis (IPF) is characterized by loss of epithelial integrity, bronchiolarization, and fibroblast activation. Basal-like cells accumulate in IPF and may promote fibrogenesis. This study investigated the role of basal cells in IPF using single-cell RNA sequencing, niche labeling, and organoid culture assays. Basal cells express WNT7A, which activates fibroblasts and inhibits type 2 alveolar epithelial cell (AEC2) renewal. Neutralizing antibodies against WNT7A or a small molecule inhibitor of Frizzled signaling attenuated lung fibrosis in mice. This study provides a new understanding of the non-stem cell function of basal cells in IPF and a potential targeting strategy for IPF.
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