Institut Curie, PSL Research University, CNRS UMR 144, Paris, France.
Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Science. 2024 Nov 29;386(6725):eadj7615. doi: 10.1126/science.adj7615.
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.
干细胞感知和响应生化和物理信号以维持内稳态。然而，干细胞如何感知其体内龛位的机械信号尚不清楚。在这项工作中，我们研究了 PIEZO 机械敏感通道在肠干细胞（ISC）龛位中的作用。我们使用小鼠遗传学和单细胞 RNA 测序分析来评估 PIEZO 通道在 ISC 维持中的必要性。体内测量基底膜硬度表明，ISC 位于隐窝底部更坚硬的微环境中。三维和二维类器官系统结合生物工程化基质和拉伸装置表明，PIEZO 通道感知细胞外机械刺激，从而调节 ISC 功能。这项研究描绘了 PIEZO 激活的机制级联，该级联协调 ISC 命运决定和维持。
