Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Sci Adv. 2023 May 24;9(21):eadc9660. doi: 10.1126/sciadv.adc9660.
Adult stem cells are essential for tissue maintenance and repair. Although genetic pathways for controlling adult stem cells are extensively investigated in various tissues, much less is known about how mechanosensing could regulate adult stem cells and tissue growth. Here, we demonstrate that shear stress sensing regulates intestine stem cell proliferation and epithelial cell number in adult . Ca imaging in ex vivo midguts shows that shear stress, but not other mechanical forces, specifically activates enteroendocrine cells among all epithelial cell types. This activation is mediated by transient receptor potential A1 (TrpA1), a Ca-permeable channel expressed in enteroendocrine cells. Furthermore, specific disruption of shear stress, but not chemical, sensitivity of TrpA1 markedly reduces proliferation of intestinal stem cells and midgut cell number. Therefore, we propose that shear stress may act as a natural mechanical stimulation to activate TrpA1 in enteroendocrine cells, which, in turn, regulates intestine stem cell behavior.
成体干细胞对于组织的维护和修复至关重要。尽管在各种组织中广泛研究了控制成体干细胞的遗传途径，但对于机械感知如何调节成体干细胞和组织生长的了解甚少。在这里，我们证明了切应力感知调节成年 肠道干细胞的增殖和上皮细胞数量。离体中肠的钙成像显示，切应力而非其他机械力，特异性地激活所有上皮细胞类型中的肠内分泌细胞。这种激活是由瞬时受体电位 A1（TRPA1）介导的，TRPA1 是一种在肠内分泌细胞中表达的钙通透性通道。此外，特异性破坏 TRPA1 的切应力敏感性，而不是化学敏感性，显著降低了肠道干细胞的增殖和中肠细胞数量。因此，我们提出切应力可能作为一种天然的机械刺激，激活肠内分泌细胞中的 TRPA1，进而调节肠道干细胞的行为。
