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TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila
Science Advances ( IF 13.6 ) Pub Date : 2023-05-24 , DOI: 10.1126/sciadv.adc9660
Jiaxin Gong 1 , Niraj K Nirala 2 , Jiazhang Chen 3 , Fei Wang 1 , Pengyu Gu 1 , Qi Wen 3 , Y Tony Ip 2 , Yang Xiang 1
Affiliation  

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 . Ca 2+ 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 2+ -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.

中文翻译:

TrpA1是调节果蝇肠道干细胞增殖的剪切应力机械传感通道

成体干细胞对于组织的维护和修复至关重要。尽管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,但人们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,我们证明剪切应力传感调节成人肠道干细胞增殖和上皮细胞数量果蝇。钙2+离体中肠成像显示,剪切应力(而非其他机械力)特异性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 Ca2+-在肠内分泌细胞中表达的渗透通道。此外,TrpA1 剪切应力的特异性破坏(而非化学敏感性)显着降低了肠干细胞的增殖和中肠细胞数量。因此,我们认为剪切应力可能作为一种自然机械刺激来激活肠内分泌细胞中的TrpA1,进而调节肠干细胞的行为。
更新日期:2023-05-24
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