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

Abstract

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.

Finding the sweet spot: glycosylation mediated regulation of intestinal inflammation

“…Functionally icGCs were shown to have a distinctive transcription profile producing a more permeable mucus that fills spatial regions between mucus plumes released from standard intestinal crypt GCs. Importantly, reduced numbers of icGCs along with disorganized mucus structure was observed during DSS colitis in mice and in the intestinal mucosa of individuals with UC highlighting important regulation of GC maturation and transcription during intestinal inflammation 88 .…”

Hyaluronan-induced alterations of the gut microbiome protects mice against Citrobacter rodentium infection and intestinal inflammation

“…The intestinal mucus layer, an important element of epithelial protection and suppression of inflammatory activity, is produced by goblet cells and plays an important role in protection against different type of injuries. 20 Therefore, goblet cell dysfunction results in reduced secretion of mucus and decreases host's ability to defend against pathogens. To determine whether hyaluronan could affect colonic goblet cell response, contributing to the observed protection, Periodic Acid Schiff (PAS) staining on the colonic sections from each mice was performed.…”

Type 2 immunity in intestinal homeostasis and inflammatory bowel disease

“…The pathogenicity associated with decreased MUC2 was linked to increased bacterial penetration in the inner layer of mucus, which may lead to intestinal inflammation and dysbiosis [ 68 ]. Single-cell transcriptional analysis identified inter-crypt goblet cells (icGCs), a functionally distinct GC subpopulation from the canonical crypt-resident GCs [ 69 ]. Mucus secreted by icGCs seals the gap between opening crypts, thus preventing microbial penetration into the stem cells niche [ 69 ].…”

“…Single-cell transcriptional analysis identified inter-crypt goblet cells (icGCs), a functionally distinct GC subpopulation from the canonical crypt-resident GCs [ 69 ]. Mucus secreted by icGCs seals the gap between opening crypts, thus preventing microbial penetration into the stem cells niche [ 69 ]. Moreover, UC patients demonstrated reduced icGCs and mucus defects [ 69 ].…”

“…Mucus secreted by icGCs seals the gap between opening crypts, thus preventing microbial penetration into the stem cells niche [ 69 ]. Moreover, UC patients demonstrated reduced icGCs and mucus defects [ 69 ]. In line with its protective role, icGC-deficient mice develop age-dependent colitis [ 69 ].…”