TY - JOUR
T1 - An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function
AU - Nyström, Elisabeth E.L.
AU - Martinez-Abad, Beatriz
AU - Arike, Liisa
AU - Birchenough, George M.H.
AU - Nonnecke, Eric B.
AU - Castillo, Patricia A.
AU - Svensson, Frida
AU - Bevins, Charles L.
AU - Hansson, Gunnar C.
AU - Johansson, Malin E.V.
N1 - Funding Information:
This work was supported by the Swedish Research Council (2015-03047, 2017-00958, and 2019-01134), the Swedish Cancer Foundation (CAN2016/487 and 2017/360), the Knut and Alice Wallenberg Foundation (2017-0028), the National Institutes of Health (U01AI095473, U01AI125926, and R37AI32738; the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH), the European Research Council (ERC) (694181), the IngaBritt and Arne Lundberg Foundation (2015-070 and 2018-0117), the Hasselblad foundation, Sahlgrenska University Hospital (ALFGBG-724681 and ALFGBG-440741), the Wilhelm and Martina Lundgren?s Foundation, and the Sahlgrenska Academy.
Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.
PY - 2021/4/16
Y1 - 2021/4/16
N2 - 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.
AB - 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.
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U2 - 10.1126/science.abb1590
DO - 10.1126/science.abb1590
M3 - Article
C2 - 33859001
AN - SCOPUS:85104483802
VL - 372
JO - Science
JF - Science
SN - 0036-8075
IS - 6539
M1 - eabb1590
ER -