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Jag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool

Author

Listed:
  • Haidi Huang

    (Shanghai Jiao Tong University)

  • Yu Jiang

    (Shanghai Jiao Tong University)

  • Jiangying Liu

    (Shanghai Jiao Tong University)

  • Dan Luo

    (Shanghai Jiao Tong University)

  • Jianghong Yuan

    (Shanghai Jiao Tong University)

  • Rongzi Mu

    (Shanghai Jiao Tong University)

  • Xiang Yu

    (Shanghai Jiao Tong University)

  • Donglei Sun

    (Shanghai Jiao Tong University)

  • Jihong Lin

    (Fujian Medical University Union Hospital)

  • Qiyue Chen

    (Fujian Medical University Union Hospital
    Fujian Medical University Union Hospital)

  • Xinjing Li

    (Shanghai Jiao Tong University)

  • Ming Jiang

    (Zhejiang University School of Medicine)

  • Jianming Xu

    (Baylor College of Medicine)

  • Bo Chu

    (Shandong University)

  • Chengqian Yin

    (Shenzhen Bay Laboratory)

  • Lei Zhang

    (Shenzhen Bay Laboratory
    Peking University Shenzhen Graduate School)

  • Youqiong Ye

    (Shanghai Jiao Tong University School of Medicine)

  • Bo Cao

    (Shanghai Jiao Tong University)

  • Qiong Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Yongchun Zhang

    (Shanghai Jiao Tong University)

Abstract

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 accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.

Suggested Citation

  • Haidi Huang & Yu Jiang & Jiangying Liu & Dan Luo & Jianghong Yuan & Rongzi Mu & Xiang Yu & Donglei Sun & Jihong Lin & Qiyue Chen & Xinjing Li & Ming Jiang & Jianming Xu & Bo Chu & Chengqian Yin & Lei , 2024. "Jag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48347-5
    DOI: 10.1038/s41467-024-48347-5
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    References listed on IDEAS

    as
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