The intestinal mucus layer, an important element of epithelial protection, is produced by goblet cells. Intestinal goblet cells are assumed to be a homogeneous cell type. In this study, however, we delineated their specific gene and protein expression profiles and identified several distinct goblet cell populations that form two differentiation trajectories. One distinct subtype, the intercrypt goblet cells (icGCs), located at the colonic luminal surface, produced mucus with properties that differed from the mucus secreted by crypt-residing goblet cells. Mice with defective icGCs had increased sensitivity to chemically induced colitis and manifested spontaneous colitis with age. Furthermore, alterations in mucus and reduced numbers of icGCs were observed in patients with both active and remissive ulcerative colitis, which highlights the importance of icGCs in maintaining functional protection of the epithelium.

肠粘液层是上皮保护的重要组成部分，由杯状细胞产生。假设肠杯状细胞是同质细胞类型。然而，在这项研究中，我们描述了它们特定的基因和蛋白质表达谱，并确定了几个不同的杯状细胞群，它们形成了两条分化轨迹。一种不同的亚型，即位于结肠腔表面的隐窝间杯状细胞 (icGCs)，其产生的粘液具有与隐窝杯状细胞分泌的粘液不同的特性。具有缺陷 icGCs 的小鼠对化学诱导的结肠炎的敏感性增加，并随着年龄的增长而表现出自发性结肠炎。此外，在活动性和缓解性溃疡性结肠炎患者中观察到粘液改变和 icGC 数量减少，