An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function

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.

Automated summary

Intestinal goblet cells are not homogeneous, with several distinct subtypes forming two differentiation trajectories. Intercrypt goblet cells located at the colonic luminal surface produce mucus with different properties from crypt-residing goblet cells. Defective icGCs in mice lead to increased sensitivity to chemically induced colitis and spontaneous colitis with age, while alterations in mucus and reduced numbers of icGCs are observed in patients with ulcerative colitis, highlighting the importance of icGCs in maintaining functional epithelial protection.