POU5F1 bridges Hedgehog signaling and epithelial remodeling in COPD.

Airway epithelium remodeling is a hallmark of chronic obstructive pulmonary disease (COPD) pathogenesis. Hedgehog signaling is activated during airway epithelial repair to warrant proliferation and during cell differentiation to establish a fully functional epithelium with optimal mucociliary clearance. Consequently, it was found to be altered in COPD patients. Using transcriptomic analysis on air-liquid interface airway epithelial cells during differentiation upon Hedgehog pathway inhibition, we highlighted potential regulators of COPD-associated epithelial remodeling. Furthermore, the alteration of POU5F1 (OCT3/4) was validated in COPD airway epithelial cells and lung tissues. Although further investigations are required, these findings uncovered essential clues tethering respiratory epithelial cell plasticity and Hedgehog signaling.