| First Author | Weiner AI | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 11 | Pages | 111805 |
| PubMed ID | 36516758 | Mgi Jnum | J:340923 |
| Mgi Id | MGI:7424710 | Doi | 10.1016/j.celrep.2022.111805 |
| Citation | Weiner AI, et al. (2022) DeltaNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury. Cell Rep 41(11):111805 |
| abstractText | The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial progenitors participate in two distinct reparative pathways: functionally beneficial regeneration via alveolar type 2 (AT2) cell proliferation and differentiation, and dysplastic tissue remodeling via intrapulmonary airway-resident basal p63(+) progenitors. Here we show that the basal cell transcription factor DeltaNp63 is required for intrapulmonary basal progenitors to participate in dysplastic alveolar remodeling following injury. We find that DeltaNp63 restricts the plasticity of intrapulmonary basal progenitors by maintaining either active or repressive histone modifications at key differentiation gene loci. Following loss of DeltaNp63, 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. |
