Department of New Biology, DGIST, Daegu, 42988, South Korea; New Biology Research Center, DGIST, Daegu, 42988, South Korea.
Department of New Biology, DGIST, Daegu, 42988, South Korea.
Biochem Biophys Res Commun. 2024 Sep 24;726:150280. doi: 10.1016/j.bbrc.2024.150280. Epub 2024 Jun 19.
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.
食管上皮是人体中最具增殖和再生能力的上皮之一，表明其具有强大的干细胞活性。然而，调节食管干细胞自我更新和分化的潜在机制仍需进一步阐明。在这里，我们确定了 YAP1 在食管干细胞中的作用。YAP1 在食管基底细胞的核中差异表达。此外，YAP1 抑制剂维替泊芬的处理干扰了食管类器官的形成。一致地，YAP1 缺失减少了食管类器官的形成和基底基因的表达，同时增加了上基基因的表达。最后，全转录组分析显示，YAP1 抑制诱导了与角质化和角化相关的基因集的显著富集，同时耗尽了与 DNA 修复和染色体维持相关的基因集。我们的数据揭示了食管干细胞的一种新的调节机制，可为食管再生医学提供一种潜在的策略。
