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TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila

Gong, Jiaxin
Nirala, Niraj K
Chen, Jiazhang
Wang, Fei
Gu, Pengyu
Wen, Qi
Ip, Y Tony
Xiang, Yang
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Abstract

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.

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Gong J, Nirala NK, Chen J, Wang F, Gu P, Wen Q, Ip YT, Xiang Y. TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila. Sci Adv. 2023 May 24;9(21):eadc9660. doi: 10.1126/sciadv.adc9660. Epub 2023 May 24. PMID: 37224252; PMCID: PMC10208578.

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10.1126/sciadv.adc9660
PubMed ID
37224252
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Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Attribution-NonCommercial 4.0 International