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

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

doi:10.1016/j.celrep.2022.110438

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

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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.

Original language	English
Pages (from-to)	110438
Journal	Cell Reports
Volume	38
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2022.110438
Publication status	Published - 01 Mar 2022

Keywords

Animals
Bone Morphogenetic Proteins/metabolism
Cell Differentiation
Enterocytes/metabolism
Goblet Cells
Intestinal Mucosa/metabolism
Intestine, Small/metabolism
Mice

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10.1016/j.celrep.2022.110438

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title = "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.",

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author = "Joep Beumer and Jens Puschhof and Yengej, {Fjodor Yousef} and Lianzheng Zhao and Adriana Martinez-Silgado and Marloes Blotenburg and Harry Begthel and Charelle Boot and {van Oudenaarden}, Alexander and Ye-Guang Chen and Hans Clevers",

year = "2022",

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doi = "10.1016/j.celrep.2022.110438",

language = "English",

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T1 - BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

AU - Beumer, Joep

AU - Puschhof, Jens

AU - Yengej, Fjodor Yousef

AU - Zhao, Lianzheng

AU - Martinez-Silgado, Adriana

AU - Blotenburg, Marloes

AU - Begthel, Harry

AU - Boot, Charelle

AU - van Oudenaarden, Alexander

AU - Chen, Ye-Guang

AU - Clevers, Hans

PY - 2022/3/1

Y1 - 2022/3/1

N2 - 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.

AB - 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.

KW - Animals

KW - Bone Morphogenetic Proteins/metabolism

KW - Cell Differentiation

KW - Enterocytes/metabolism

KW - Goblet Cells

KW - Intestinal Mucosa/metabolism

KW - Intestine, Small/metabolism

KW - Mice

U2 - 10.1016/j.celrep.2022.110438

DO - 10.1016/j.celrep.2022.110438

M3 - Article

C2 - 35235783

SN - 2211-1247

VL - 38

SP - 110438

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -

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

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Keywords

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