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    Intestinal epithelial cells derive from stem cells at the crypt base and travel along the crypt-villus axis to die at the villus tip. The two dominant villus epithelial cell types, absorptive enterocytes and mucous-secreting goblet cells, are mature when they exit crypts. Murine enterocytes switch functional cell states during migration along the villus. Here, we ask whether this zonation is driven by the bone morphogenetic protein (BMP) gradient, which increases toward the villus. Using human intestinal organoids, we show that BMP signaling controls the expression of zonated genes in enterocytes. We find that goblet cells display similar zonation involving antimicrobial genes. Using an inducible Bmpr1a knockout mouse model, we confirm that BMP controls these zonated genes in vivo. Our findings imply that local manipulation of BMP signal strength may be used to reset the enterocyte "rheostat" of carbohydrate versus lipid uptake and to control the antimicrobial response through goblet cells. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

    Citation

    Joep Beumer, Jens Puschhof, Fjodor Yousef Yengej, Lianzheng Zhao, Adriana Martinez-Silgado, Marloes Blotenburg, Harry Begthel, Charelle Boot, Alexander van Oudenaarden, Ye-Guang Chen, Hans Clevers. BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states. Cell reports. 2022 Mar 01;38(9):110438

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    PMID: 35235783

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