Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells
Shivaraju Manjunatha,Chitta Udbhav K,Grange Robert M H et al. Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells.[J] .Science, 2021, 371: 52-57.
Neuroendocrine (NE) cells are epithelial cells that possess many of the characteristics of neurons, including the presence of secretory vesicles and the ability to sense environmental stimuli. The normal physiologic functions of solitary airway NE cells remain a mystery. We show that mouse and human airway basal stem cells sense hypoxia. Hypoxia triggers the direct differentiation of these stem cells into solitary NE cells. Ablation of these solitary NE cells during hypoxia results in increased epithelial injury, whereas the administration of the NE cell peptide CGRP rescues this excess damage. Thus, we identify stem cells that directly sense hypoxia and respond by differentiating into solitary NE cells that secrete a protective peptide that mitigates hypoxic injury.
52-57.神經內分泌（NE）細胞是上皮細胞，具有神經元的許多特徵，包括分泌囊泡的存在和感知環境刺激的能力。孤立的氣道NE細胞的正常生理功能仍然是一個謎。我們表明，小鼠和人的氣道基底幹細胞感知缺氧。缺氧觸發這些幹細胞直接分化為單獨的NE細胞。缺氧期間這些孤立的NE細胞的消融導致上皮損傷的增加，而NE細胞肽CGRP的給藥可以挽救這種過度的損傷。因此，我們確定了直接感知缺氧並通過分化成能減輕缺氧損傷的保護性肽的孤立性NE細胞分化而做出反應的幹細胞。。
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