biostudies-literatureHuang HNatural Science Foundation of ShanghaiNational Natural Science Foundation of ChinaNatural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)National Natural Science Foundation of China (National Science Foundation of China)4124https://www.ebi.ac.uk/biostudies/studies/S-EPMC11096375biostudies-literatureUnknown15(1)Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accNature communicationsJag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool.PMC1109637522ZR143530031771512Liu JChen QHuang HZhang LJiang MYe YYuan JXu JCao BLuo DJiang YLi XChu BWang QYin CZhang YSun DLin JMu RYu XfalseJag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool.Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and acc2024-01-01T00:00:00Z2024 May2026-06-03T04:59:59.16Z2026-05-28T03:06:40.792ZS-EPMC110963753875002610.1038/s41467-024-48347-5