ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury
Aaron I. Weiner, Gan Zhao, Hanna M. Zayas, Nicolas P. Holcomb, Stephanie Adams‐Tzivelekidis, Joanna Wong, Maria E. Gentile, Dyuthi Reddy, Joey Wei, Gargi Palashikar, Kwaku Quansah, Andrew E. Vaughan
Abstract
progenitors. Here we show that the basal cell transcription factor ΔNp63 is required for intrapulmonary basal progenitors to participate in dysplastic alveolar remodeling following injury. We find that ΔNp63 restricts the plasticity of intrapulmonary basal progenitors by maintaining either active or repressive histone modifications at key differentiation gene loci. Following loss of ΔNp63, intrapulmonary basal progenitors are capable of either airway or alveolar differentiation depending on their surrounding environment both in vitro and in vivo. Uncovering these regulatory mechanisms of dysplastic repair and lung basal cell fate choice highlight potential therapeutic targets to promote functional alveolar regeneration following severe lung injuries.