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

• DOI: 10.1126/science.adj7615
• Publication Date: 2024-11-28T19:00:56Z
• Authors: Meryem B. Baghdadi; Ronja M. Houtekamer; Louisiane Perrin; Abilasha Rao-Bhatia; Myles Whelen; Linda Decker; Martin Bergert; Carlos Pérez-Gonz...; Réda Bouras; Giacomo Gropplero; Adrian K. H. Loe; Amin Afkhami-Poos...; Xin Chen; Xi Huang; Stephanie Descroix; Jeffrey L. Wrana; Alba Diz-Muñoz; Martijn Gloerich; Arshad Ayyaz; Danijela Matic Vi...; Tae-Hee Kim
• Keywords: 0301 basic medicine; 0303 health sciences; General

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.