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

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabb1590
Author(s):  
Elisabeth E. L. Nyström ◽  
Beatriz Martinez-Abad ◽  
Liisa Arike ◽  
George M. H. Birchenough ◽  
Eric B. Nonnecke ◽  
...  

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.

2021 ◽  
Vol 22 (24) ◽  
pp. 13642
Author(s):  
Hassan Melhem ◽  
Daniel Regan-Komito ◽  
Jan Hendrik Niess

Maintaining intestinal health requires clear segregation between epithelial cells and luminal microbes. The intestinal mucus layer, produced by goblet cells (GCs), is a key element in maintaining the functional protection of the epithelium. The importance of the gut mucus barrier is highlighted in mice lacking Muc2, the major form of secreted mucins. These mice show closer bacterial residence to epithelial cells, develop spontaneous colitis and became moribund when infected with the attaching and effacing pathogen, Citrobacter rodentium. Furthermore, numerous observations have associated GCs and mucus layer dysfunction to the pathogenesis of inflammatory bowel disease (IBD). However, the molecular mechanisms that regulate the physiology of GCs and the mucus layer remain obscured. In this review, we consider novel findings describing divergent functionality and expression profiles of GCs subtypes within intestinal crypts. We also discuss internal (host) and external (diets and bacteria) factors that modulate different aspects of the mucus layer as well as the contribution of an altered mucus barrier to the onset of IBD.


2019 ◽  
Vol 129 (9) ◽  
pp. 871-881 ◽  
Author(s):  
Han-Chung Lee ◽  
Hadri Hadi Md Yusof ◽  
Melody Pui-Yee Leong ◽  
Shahidee Zainal Abidin ◽  
Eryse Amira Seth ◽  
...  

2002 ◽  
Vol 6 (1) ◽  
pp. 39-60 ◽  
Author(s):  
Alex S. Beliaev ◽  
Dorothea K. Thompson ◽  
Tripti Khare ◽  
Hanjo Lim ◽  
Craig C. Brandt ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163561 ◽  
Author(s):  
Shuji Hamauchi ◽  
Hideo Shichinohe ◽  
Haruto Uchino ◽  
Shigeru Yamaguchi ◽  
Naoki Nakayama ◽  
...  

2006 ◽  
Vol 72 (9) ◽  
pp. 6331-6344 ◽  
Author(s):  
Karuna Chourey ◽  
Melissa R. Thompson ◽  
Jennifer Morrell-Falvey ◽  
Nathan C. VerBerkmoes ◽  
Steven D. Brown ◽  
...  

ABSTRACT The biological impact of 24-h (“chronic”) chromium(VI) [Cr(VI) or chromate] exposure on Shewanella oneidensis MR-1 was assessed by analyzing cellular morphology as well as genome-wide differential gene and protein expression profiles. Cells challenged aerobically with an initial chromate concentration of 0.3 mM in complex growth medium were compared to untreated control cells grown in the absence of chromate. At the 24-h time point at which cells were harvested for transcriptome and proteome analyses, no residual Cr(VI) was detected in the culture supernatant, thus suggesting the complete uptake and/or reduction of this metal by cells. In contrast to the untreated control cells, Cr(VI)-exposed cells formed apparently aseptate, nonmotile filaments that tended to aggregate. Transcriptome profiling and mass spectrometry-based proteomic characterization revealed that the principal molecular response to 24-h Cr(VI) exposure was the induction of prophage-related genes and their encoded products as well as a number of functionally undefined hypothetical genes that were located within the integrated phage regions of the MR-1 genome. In addition, genes with annotated functions in DNA metabolism, cell division, biosynthesis and degradation of the murein (peptidoglycan) sacculus, membrane response, and general environmental stress protection were upregulated, while genes encoding chemotaxis, motility, and transport/binding proteins were largely repressed under conditions of 24-h chromate treatment.


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