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

• 成果类型: Article
• 署名作者: Baghdadi, Meryem B.; Houtekamer, Ronja M.; Perrin, Louisiane; Rao-Bhatia, Abilasha; Whelen, Myles; Decker, Linda; Bergert, Martin; Perez-Gonzalez, Carlos; Bouras, Reda; Gropplero, Giacomo; Loe, Adrian K. H.; Afkhami-Poostchi, Amin; Chen, Xin; Huang, Xi; Descroix, Stephanie; Wrana, Jeffrey L.; Diz-Munoz, Alba; Gloerich, Martijn; Ayyaz, Arshad; Matic Vignjevic, Danijela; Kim, Tae-Hee
• 署名单位: Sorbonne Universite; Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); University of Toronto; Hospital for Sick Children (SickKids); Utrecht University; Utrecht University Medical Center; University of Toronto; University of Calgary; University of Calgary; European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite PSL; UNICANCER; Institut Curie; Sorbonne Universite; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Saint Michaels Hospital Toronto
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8313
• DOI: 10.1126/science.adj7615
• 发表日期: 2024-11-29
• 关键词: activated ion-channel; notch; differentiation; proliferation; migration; reveals; tension; forces; math1

摘要

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.