SPDEF and chronic obstructive pulmonary disease: Aside from Notch abnormal reactivation, aberrant WNT/β-catenin reactivation also contributes to impaired epithelial cell differentiation reminiscent of COPD, as extrinsic activation of WNT/β-catenin in ALI-HBEC increased SPDEF gene expression while suppressing expression of ciliated cells-associated genes FOXJ1 and MCIDAS (Malleske et al., 2018; Carlier et al., 2020).