YAP1 regulates esophageal stem cells' self-renewal and differentiation

Area of Science:

• Gastroenterology
• Stem Cell Biology
• Molecular Biology

Background:

• The esophageal epithelium exhibits high proliferative and regenerative capacity, driven by stem cells.
• Mechanisms governing esophageal stem cell self-renewal and differentiation remain incompletely understood.

Purpose of the Study:

• To investigate the role of YAP1 (Yes-associated protein 1) in regulating esophageal stem cell function.
• To elucidate the molecular mechanisms underlying YAP1's involvement in esophageal epithelial homeostasis.

Main Methods:

• Localization of YAP1 in esophageal basal cells.
• Pharmacological inhibition of YAP1 using verteporfin in esophageal organoid models.
• Genetic deletion of YAP1 in esophageal stem cells.
• Global transcriptomic analysis to assess gene expression changes.

Main Results:

• YAP1 is localized in the nuclei of esophageal basal cells.
• Verteporfin treatment and YAP1 deletion significantly impaired esophageal organoid formation.
• YAP1 inhibition led to decreased expression of basal cell markers and increased expression of suprabasal markers.
• Transcriptomic analysis revealed YAP1 inhibition enriched keratinization/cornification pathways and depleted DNA repair/chromosome maintenance pathways.

Conclusions:

• YAP1 plays a critical role in maintaining esophageal stem cell identity and regulating differentiation.
• YAP1 inhibition promotes a switch towards terminal differentiation and keratinization.
• These findings highlight a novel regulatory mechanism for esophageal stem cells with potential applications in regenerative medicine.