Submission 108
Role of PIEZO mechanosensitive channels in intestinal stem cells
S7-03-Oral Short Talk
Presented by: Meryem Baghdadi
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.