Epithelial tension controls intestinal cell extrusion

Daniel Krueger; Willem Kasper Spoelstra; Dirk Jan Mastebroek; Rutger N.U. Kok; Shanie Wu; Mike Nikolaev; Marie Bannier-Hélaouët; Nikolche Gjorevski; Matthias Lutolf; Johan van Es; Jeroen van Zon; Sander J. Tans; Hans Clevers

doi:10.1126/science.adr8753

Epithelial tension controls intestinal cell extrusion

Daniel Krueger^*
, Willem Kasper Spoelstra
, Dirk Jan Mastebroek
, Rutger N.U. Kok
, Shanie Wu
, Mike Nikolaev
, Marie Bannier-Hélaouët
, Nikolche Gjorevski
, Matthias Lutolf
, Johan van Es
, Jeroen van Zon^*
, Sander J. Tans^*
, Hans Clevers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In this study, we found instead that a local “tug-of-war” competition between contractile cells regulated extrusion in the intestinal epithelium. We combined quantitative live microscopy, optogenetic induction of tissue tension, genetic perturbation of myosin II activity, and local disruption of the basal cortex in mouse intestines and intestinal organoids. these approaches revealed that a dynamic actomyosin network generates tension throughout the intestinal villi, including the villus tip region. mechanically weak cells unable to maintain this tension underwent extrusion. thus, epithelial barrier integrity depends on intercellular mechanics.

Original language	English
Article number	eadr8753
Journal	Science
Volume	389
Issue number	6764
DOIs	https://doi.org/10.1126/science.adr8753
Publication status	Published - 4 Sept 2025

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title = "Epithelial tension controls intestinal cell extrusion",

abstract = "Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In this study, we found instead that a local “tug-of-war” competition between contractile cells regulated extrusion in the intestinal epithelium. We combined quantitative live microscopy, optogenetic induction of tissue tension, genetic perturbation of myosin II activity, and local disruption of the basal cortex in mouse intestines and intestinal organoids. these approaches revealed that a dynamic actomyosin network generates tension throughout the intestinal villi, including the villus tip region. mechanically weak cells unable to maintain this tension underwent extrusion. thus, epithelial barrier integrity depends on intercellular mechanics.",

author = "Daniel Krueger and Spoelstra, \{Willem Kasper\} and Mastebroek, \{Dirk Jan\} and Kok, \{Rutger N.U.\} and Shanie Wu and Mike Nikolaev and Marie Bannier-H{\'e}laou{\"e}t and Nikolche Gjorevski and Matthias Lutolf and \{van Es\}, Johan and \{van Zon\}, Jeroen and Tans, \{Sander J.\} and Hans Clevers",

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doi = "10.1126/science.adr8753",

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T1 - Epithelial tension controls intestinal cell extrusion

AU - Krueger, Daniel

AU - Spoelstra, Willem Kasper

AU - Mastebroek, Dirk Jan

AU - Kok, Rutger N.U.

AU - Wu, Shanie

AU - Nikolaev, Mike

AU - Bannier-Hélaouët, Marie

AU - Gjorevski, Nikolche

AU - Lutolf, Matthias

AU - van Es, Johan

AU - van Zon, Jeroen

AU - Tans, Sander J.

AU - Clevers, Hans

PY - 2025/9/4

Y1 - 2025/9/4

N2 - Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In this study, we found instead that a local “tug-of-war” competition between contractile cells regulated extrusion in the intestinal epithelium. We combined quantitative live microscopy, optogenetic induction of tissue tension, genetic perturbation of myosin II activity, and local disruption of the basal cortex in mouse intestines and intestinal organoids. these approaches revealed that a dynamic actomyosin network generates tension throughout the intestinal villi, including the villus tip region. mechanically weak cells unable to maintain this tension underwent extrusion. thus, epithelial barrier integrity depends on intercellular mechanics.

AB - Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In this study, we found instead that a local “tug-of-war” competition between contractile cells regulated extrusion in the intestinal epithelium. We combined quantitative live microscopy, optogenetic induction of tissue tension, genetic perturbation of myosin II activity, and local disruption of the basal cortex in mouse intestines and intestinal organoids. these approaches revealed that a dynamic actomyosin network generates tension throughout the intestinal villi, including the villus tip region. mechanically weak cells unable to maintain this tension underwent extrusion. thus, epithelial barrier integrity depends on intercellular mechanics.

UR - https://www.scopus.com/pages/publications/105015182032

U2 - 10.1126/science.adr8753

DO - 10.1126/science.adr8753

M3 - Article

AN - SCOPUS:105015182032

SN - 0036-8075

VL - 389

JO - Science

JF - Science

IS - 6764

M1 - eadr8753

ER -

Epithelial tension controls intestinal cell extrusion

Abstract

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