TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila.
TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila.
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DOI：
10.1126/sciadv.adc9660
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发表时间：
2023-05-24
期刊：
影响因子：
13.6
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中科院分区：
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--
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成体干细胞对于组织维护和修复至关重要。虽然控制成体干细胞的遗传途径在各种组织中得到了广泛的研究，但对机械传感如何调节成体干细胞和组织生长知之甚少。在这里，我们表明，剪切应力感应调节肠干细胞增殖和上皮细胞数量在成年果蝇。离体中肠的Ca2+成像显示，剪切应力，而不是其他机械力，特异性地激活所有上皮细胞类型中的肠内分泌细胞。这种激活由瞬时受体电位A1（TrpA1）介导，这是一种在肠内分泌细胞中表达的Ca2+渗透通道。此外，剪切应力的特异性破坏，而不是化学，TrpA1的敏感性显着降低肠干细胞和中肠细胞数量的增殖。因此，我们认为切应力可能作为一种自然的机械刺激来激活肠内分泌细胞中的TrpA1，从而调节肠干细胞的行为。肠内分泌细胞中TrpA1对剪切应力的感知调节果蝇中肠的肠干细胞增殖。
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 Drosophila. Ca2+ 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 Ca2+-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. Shear stress sensing by TrpA1 in enteroendocrine cells regulates intestinal stem cell proliferation in the Drosophila midgut.
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