YAP1 regulates esophageal stem cells' self-renewal and differentiation.

Esophageal epithelium is one of the most proliferative and regenerative epithelia in our body, indicating robust stem cell activity. However, the underlying mechanisms regulating the self-renewal and differentiation of esophageal stem cells need to be more elucidated. Here, we identify the role of YAP1 in esophageal stem cells. YAP1 is differentially expressed in the nuclei of esophageal basal cells. Furthermore, the treatment of verteporfin, a YAP1 inhibitor, interfered with esophageal organoid formation. Consistently, YAP1 deletion decreased esophageal organoid formation and the expression of basal genes while increasing the expression of suprabasal genes. Finally, global transcriptomic analysis revealed that YAP1 inhibition induced a significant enrichment of gene sets related to keratinization and cornification, while depleting gene sets related to DNA repair and chromosome maintenance. Our data uncover a novel regulatory mechanism for esophageal stem cells, which could provide a potential strategy for esophageal regenerative medicine.

Establishment of a chemical tongue injury-recovery mouse model.

Tongue epithelium is one of the most proliferative and regenerative epithelia in our body. However, tongue stem cell research is hampered partly by the lack of optimal animal models to study tongue injury, repair, and regeneration. Here, we establish a novel chemically induced tongue injury-recovery mouse model. Focal application of sodium hydroxide for a limited time led to the denudation of suprabasal layers, leaving the basal layer. Time course study revealed that tongue epithelial cells robustly proliferate over one week after the tongue injury. Importantly, we demonstrated that our novel mouse model could be employed in the lineage tracing of the tongue stem cells under the injury and repair process and further showed that tongue stem cells proliferate faster and generate larger clones in the injury condition than in the steady state condition. Our data indicate the development of a novel chemically induced tongue injury-recovery mouse model for tongue stem cell research, which will significantly facilitate the preclinical study for the pathogenesis and treatment of caustic ingestion.