PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance
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.
Authors
- Xin Chen (ORCID: https://orcid.org/0000-0001-7620-5975)
- Abilasha Rao‐Bhatia (ORCID: https://orcid.org/0000-0002-6637-4545)
- Linda Decker (ORCID: https://orcid.org/0000-0001-5495-2611)
- Ronja M. Houtekamer (ORCID: https://orcid.org/0000-0001-6174-1134)
- Stéphanie Descroix (ORCID: https://orcid.org/0000-0003-0027-352X)
- Adrian Kwan Ho Loe (ORCID: https://orcid.org/0000-0002-1021-4657)
- Carlos Pérez‐González (ORCID: https://orcid.org/0000-0002-1794-0299)
- Amin Afkhami-Poostchi (ORCID: https://orcid.org/0000-0001-7224-239X)
- Martin Bergert (ORCID: https://orcid.org/0000-0002-3222-8929)
- Louisiane Perrin (ORCID: https://orcid.org/0000-0001-5691-3229)
- Jeffrey L. Wrana (ORCID: https://orcid.org/0000-0003-0932-0644)
- Danijela Matic Vignjevic (ORCID: https://orcid.org/0000-0003-4250-703X)
- Arshad Ayyaz (ORCID: https://orcid.org/0009-0004-8573-2012)
- Xi Huang (ORCID: https://orcid.org/0000-0002-7177-7525)
- Giacomo Gropplero (ORCID: https://orcid.org/0000-0002-8328-9000)
- Martijn Gloerich (ORCID: https://orcid.org/0000-0002-0034-4642)
- Alba Diz-Muñoz (ORCID: https://orcid.org/0000-0001-6864-8901)
- Tae-Hee Kim (ORCID: https://orcid.org/0000-0002-4872-1742)
- Meryem B. Baghdadi (ORCID: https://orcid.org/0000-0002-9286-6922)
- Myles Whelen (ORCID: https://orcid.org/0009-0003-8563-7069)
- Réda Bouras
Institutions
- Mount Sinai Hospital (CA)
- Centre National de la Recherche Scientifique (FR)
- St. Michael's Hospital (CA)
- University of Calgary (CA)
- University of Toronto (CA)
- Utrecht University (NL)
- Lunenfeld-Tanenbaum Research Institute (CA)
- Université Paris Sciences et Lettres (FR)
- Hospital for Sick Children (CA)
- University Medical Center Utrecht (NL)
- European Molecular Biology Laboratory (DE)
- SickKids Foundation (CA)
- Biologie cellulaire et Cancer (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Science
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1126/science.adj7615
- Citations
- 77
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 24.82