肠上皮稳态对人体健康至关重要，其紊乱可以导致包括肠道炎症和结肠癌在内多种疾病的发生。肠上皮稳态的维持需要肠上皮细胞有序而精准的命运决定，以及肠上皮细胞功能的良好运转。我们的前期工作发现，Emc3在肠上皮特异性敲除可以导致小鼠体重增长缓慢，长期生存率降低，潘氏细胞严重缺失，杯状细胞黏蛋白分泌减少，以及肠上皮细胞内质网应激反应激活等多种表型。本项目将在此基础上深入探究Emc3在小肠上皮细胞命运决定和功能维持中的作用，并以Emc3为重要切入点，阐释内质网动态平衡及紊乱应激对潘氏细胞定向分化、杯状细胞黏蛋白分泌以及肠上皮干细胞干性维持的关键作用及分子机制。同时，我们还将揭示Emc3在急性结肠炎发生及病后修复中的作用。本项目的实施将全面加深我们对小肠上皮细胞命运决定和功能维持方式的理解，并为治疗肠道炎症等肠上皮强关联性疾病提供重要理论基础和潜在的干预靶点。

Intestinal epithelial homeostasis is crucial for human health. Its disturbance can lead to various diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Intestinal epithelial homeostasis maintenance requires sequential and accurate cell differentiation or fate determination, as well as the delicate working of intestinal epithelium. Our previous work has revealed that intestinal epithelium specific knockout of Emc3 gene generated interesting phenotypes in mice: lower growth rate in weight, reduced long-term survival rate, severe loss of Paneth cells, reduced secretory mucin glycoproteins by goblet cells, and endoplasmic reticulum stress of intestinal epithelium. In this project, we will further investigate the role of Emc3 in intestinal epithelium cell fate determination and function maintenance. We will focus on the molecular mechanism of how endoplasmic reticulum dynamic balance and stress response contribute to Paneth cell differentiation, goblet cell mucin glycoproteins secretion, and intestinal stem cell stemness maintenance. In addition, the roles of Emc3 in acute colitis and followed recovery will be explored. This work will broaden our understanding of fate determination and function maintenance of intestinal epithelium, and lay theoretical foundation for the treatment of IBD and other intestinal epithelium related diseases.