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

First Author  Baghdadi MB Year  2024
Journal  Science Volume  386
Issue  6725 Pages  eadj7615
PubMed ID  39607940 Mgi Jnum  J:362874
Mgi Id  MGI:7788901 Doi  10.1126/science.adj7615
Citation  Baghdadi MB, et al. (2024) PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance. Science 386(6725):eadj7615
abstractText  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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