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BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Authors: Joep Beumer; Jens Puschhof; Fjodor Yousef Yengej; Lianzheng Zhao; Adriana Martinez-Silgado; Marloes Blotenburg; Harry Begthel; +4 Authors

BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Abstract

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.

Country
Netherlands
Keywords

BMP signaling, Small/metabolism, General Biochemistry,Genetics and Molecular Biology, single-cell RNA sequencing, Mice, Intestine, Small, Journal Article, Animals, Intestinal Mucosa, Intestine, Small/metabolism, organoids, Enterocytes/metabolism, Research Support, Non-U.S. Gov't, Bone Morphogenetic Proteins/metabolism, Cell Differentiation, intestinal differentiation, Intestine, Enterocytes, Bone Morphogenetic Proteins, enterocytes, Goblet Cells, CRISPR-Cas9, Intestinal Mucosa/metabolism

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    103
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
103
Top 1%
Top 10%
Top 1%
Green
gold