作为哺乳动物体内小肠上皮细胞持续快速更新的驱动力量，小肠干细胞通常受肠道上皮微环境中多种信号通路协同调控，如WNT、BMP、NOTCH等信号通路。然而，非经典TGF-beta信号通路在小肠干细胞稳态调控中的作用及其分子机制仍不清楚。在前期工作中，我们利用小肠类器官体外培养模型发现非经典TGF-beta信号通路可抑制小肠干细胞的干性及影响组织稳态。因此，本项目将利用小鼠及类器官模型，继续深入研究非经典TGF-beta信号通路对小肠干细胞稳态的调控作用，并阐明其具体的分子作用机制，同时探讨此信号通路在肠道稳态异常导致的肠道肿瘤发生发展过程中的作用。该研究将进一步丰富我们对肠道上皮稳态调控机制的认识，以期为相关肠道疾病的治疗提供新的理论基础和潜在治疗靶点。

The intestinal stem cells, as the driving force for the continuous and rapid renewal of the intestine epithelial in mammals, are usually regulated by various signaling pathways in intestinal epithelial microenvironment, such as WNT signaling, BMP signaling, NOTCH signaling and others. However, the role and mechanism of non-canonical TGF-beta signaling pathway in regulating the homeostasis of intestinal stem cells are still unclear. In the previous work, we established the ex-vivo system of culturing intestinal organoids and found that non-canonical TGF-beta signaling pathway inhibited the stemness of intestinal stem cells and influenced tissue homeostasis. This project will combine mouse models and intestinal organoids to further study the role of non-canonical TGF-beta signaling pathway in regulating the homeostasis of intestinal stem cells, elucidate the underlying molecular mechanism, and address the role of non-canonical TGF-beta signaling pathway in the occurrence and progression of intestinal tumors caused by the deterioration of intestinal homeostasis. This research will further enrich our understanding of the regulation mechanism of intestinal epithelial homeostasis and expect to provide new theoretical basis and potential therapeutic targets for the treatment of related intestinal diseases.