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Research Highlight
Airing out the stem cell niche
Development 2021 148: e0403
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Oxygen levels are known to influence stem cell niches, but exactly how they govern the behaviour of stem cells, particularly epithelial stem cells, is unclear. Now, Hidemitsu Harada and colleagues propose that oxygen regulates epithelial stem cell proliferation in the mouse incisor by regulating RhoA-actomyosin-YAP/TAZ signalling. The mouse incisor grows continuously throughout the life of the animal, and this growth is driven by slow-cycling cells (SCCs) within the dental epithelium that give rise to transit-amplifying cells (TACs). The authors first show that, compared with TACs, SCCs within the incisor are situated further away from blood vessels, suggesting that they are maintained in hypoxic conditions. By culturing mouse incisors and mHAT9d dental epithelial cells in vitro, the authors further show that hypoxia restrains cell proliferation and reduces YAP/TAZ activity, and increases levels of HIF1α and active RhoA in dental epithelial cells. Following this, they report that a hypoxia-RhoA signal is involved in maintaining cortical actomyosin and adherens junctions in mHAT9d cells. Finally, they reveal that inhibiting RhoA/ROCK activity increases cell proliferation and YAP/TAZ activity, suggesting that RhoA-mediated cortical actomyosin acts to restrain cell proliferation in dental epithelial cells through YAP/TAZ signalling. Overall, these findings highlight the importance of blood vessel geometry within stem cell niches and uncover key links between hypoxia, RhoA and YAP/TAZ signalling.

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