PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance

Meryem B. Baghdadi; Ronja M. Houtekamer; Louisiane Perrin; Abilasha Rao-Bhatia; Myles Whelen; Linda Decker; Martin Bergert; Carlos Pérez-Gonzàlez; Réda Bouras; Giacomo Gropplero; Adrian K.H. Loe; Amin Afkhami-Poostchi; Xin Chen; Xi Huang; Stephanie Descroix; Jeffrey L. Wrana; Alba Diz-Muñoz; Martijn Gloerich; Arshad Ayyaz; Danijela Matic Vignjevic; Tae Hee Kim

doi:10.1126/science.adj7615

PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance

Meryem B. Baghdadi^*, Ronja M. Houtekamer, Louisiane Perrin, Abilasha Rao-Bhatia, Myles Whelen, Linda Decker, Martin Bergert, Carlos Pérez-Gonzàlez, Réda Bouras, Giacomo Gropplero, Adrian K.H. Loe, Amin Afkhami-Poostchi, Xin Chen, Xi Huang, Stephanie Descroix, Jeffrey L. Wrana, Alba Diz-Muñoz, Martijn Gloerich, Arshad Ayyaz, Danijela Matic Vignjevic^*Tae Hee Kim^*

^*Corresponding author for this work

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

Abstract

Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels in the intestinal stem cell (ISC) niche. We used mouse genetics and single-cell RNA sequencing analysis to assess the requirement for PIEZO channels in ISC maintenance. In vivo measurement of basement membrane stiffness showed that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Three-dimensional and two-dimensional organoid systems combined with bioengineered substrates and a stretching device revealed that PIEZO channels sense extracellular mechanical stimuli to modulate ISC function. This study delineates the mechanistic cascade of PIEZO activation that coordinates ISC fate decision and maintenance.

Original language	English
Article number	eadj7615
Journal	Science (New York, N.Y.)
Volume	386
Issue number	6725
DOIs	https://doi.org/10.1126/science.adj7615
Publication status	Published - 29 Nov 2024

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Baghdadi, M. B., Houtekamer, R. M., Perrin, L., Rao-Bhatia, A., Whelen, M., Decker, L., Bergert, M., Pérez-Gonzàlez, C., Bouras, R., Gropplero, G., Loe, A. K. H., Afkhami-Poostchi, A., Chen, X., Huang, X., Descroix, S., Wrana, J. L., Diz-Muñoz, A., Gloerich, M., Ayyaz, A., ... Kim, T. H. (2024). PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance. Science (New York, N.Y.), 386(6725), Article eadj7615. https://doi.org/10.1126/science.adj7615

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title = "PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance",

abstract = "Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels in the intestinal stem cell (ISC) niche. We used mouse genetics and single-cell RNA sequencing analysis to assess the requirement for PIEZO channels in ISC maintenance. In vivo measurement of basement membrane stiffness showed that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Three-dimensional and two-dimensional organoid systems combined with bioengineered substrates and a stretching device revealed that PIEZO channels sense extracellular mechanical stimuli to modulate ISC function. This study delineates the mechanistic cascade of PIEZO activation that coordinates ISC fate decision and maintenance.",

author = "Baghdadi, {Meryem B.} and Houtekamer, {Ronja M.} and Louisiane Perrin and Abilasha Rao-Bhatia and Myles Whelen and Linda Decker and Martin Bergert and Carlos P{\'e}rez-Gonz{\`a}lez and R{\'e}da Bouras and Giacomo Gropplero and Loe, {Adrian K.H.} and Amin Afkhami-Poostchi and Xin Chen and Xi Huang and Stephanie Descroix and Wrana, {Jeffrey L.} and Alba Diz-Mu{\~n}oz and Martijn Gloerich and Arshad Ayyaz and {Matic Vignjevic}, Danijela and Kim, {Tae Hee}",

year = "2024",

month = nov,

day = "29",

doi = "10.1126/science.adj7615",

language = "English",

volume = "386",

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Baghdadi, MB, Houtekamer, RM, Perrin, L, Rao-Bhatia, A, Whelen, M, Decker, L, Bergert, M, Pérez-Gonzàlez, C, Bouras, R, Gropplero, G, Loe, AKH, Afkhami-Poostchi, A, Chen, X, Huang, X, Descroix, S, Wrana, JL, Diz-Muñoz, A, Gloerich, M, Ayyaz, A, Matic Vignjevic, D & Kim, TH 2024, 'PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance', Science (New York, N.Y.), vol. 386, no. 6725, eadj7615. https://doi.org/10.1126/science.adj7615

TY - JOUR

T1 - PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance

AU - Baghdadi, Meryem B.

AU - Houtekamer, Ronja M.

AU - Perrin, Louisiane

AU - Rao-Bhatia, Abilasha

AU - Whelen, Myles

AU - Decker, Linda

AU - Bergert, Martin

AU - Pérez-Gonzàlez, Carlos

AU - Bouras, Réda

AU - Gropplero, Giacomo

AU - Loe, Adrian K.H.

AU - Afkhami-Poostchi, Amin

AU - Chen, Xin

AU - Huang, Xi

AU - Descroix, Stephanie

AU - Wrana, Jeffrey L.

AU - Diz-Muñoz, Alba

AU - Gloerich, Martijn

AU - Ayyaz, Arshad

AU - Matic Vignjevic, Danijela

AU - Kim, Tae Hee

PY - 2024/11/29

Y1 - 2024/11/29

N2 - Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels in the intestinal stem cell (ISC) niche. We used mouse genetics and single-cell RNA sequencing analysis to assess the requirement for PIEZO channels in ISC maintenance. In vivo measurement of basement membrane stiffness showed that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Three-dimensional and two-dimensional organoid systems combined with bioengineered substrates and a stretching device revealed that PIEZO channels sense extracellular mechanical stimuli to modulate ISC function. This study delineates the mechanistic cascade of PIEZO activation that coordinates ISC fate decision and maintenance.

AB - Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels in the intestinal stem cell (ISC) niche. We used mouse genetics and single-cell RNA sequencing analysis to assess the requirement for PIEZO channels in ISC maintenance. In vivo measurement of basement membrane stiffness showed that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Three-dimensional and two-dimensional organoid systems combined with bioengineered substrates and a stretching device revealed that PIEZO channels sense extracellular mechanical stimuli to modulate ISC function. This study delineates the mechanistic cascade of PIEZO activation that coordinates ISC fate decision and maintenance.

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U2 - 10.1126/science.adj7615

DO - 10.1126/science.adj7615

M3 - Article

C2 - 39607940

AN - SCOPUS:85211202469

SN - 0036-8075

VL - 386

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6725

M1 - eadj7615

ER -

PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance

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