Protecting the lung from hypoxic stress The lung experiences constantly changing oxygen concentrations and must recognize and respond to a low-oxygen environment. Shivaraju et al. reveal that airway stem cells directly sense hypoxia and respond by differentiating into protective neuroendocrine (NE) cells that secrete a peptide that mitigates tissue damage (see the Perspective by Zacharias). This work suggests that the observed NE cell hyperplasia that accompanies lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease represents a compensatory physiologic response. More broadly, it raises the possibility that stem cells throughout the body sense hypoxia and differentiate into organ-specific NE cells. Science, this issue p. 52; see also p. 32 Solitary neuroendocrine cells in the murine trachea provide a protective role during hypoxic stress. 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.

中文翻译：

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气道干细胞感知缺氧并分化为保护性孤立神经内分泌细胞

保护肺部免受缺氧应激 肺部经历不断变化的氧气浓度，必须识别低氧环境并对其做出反应。希瓦拉朱等人。揭示气道干细胞直接感知缺氧并通过分化为保护性神经内分泌（NE）细胞来做出反应，这些细胞分泌一种减轻组织损伤的肽（参见Zacharias的观点）。这项工作表明，观察到的伴随哮喘、囊性纤维化和慢性阻塞性肺病等肺部疾病的 NE 细胞增生代表了一种代偿性生理反应。更广泛地说，它提出了全身干细胞感知缺氧并分化为器官特异性 NE 细胞的可能性。科学，本期第 14 页。52；另见 p. 32 小鼠气管中的孤立神经内分泌细胞在缺氧应激期间发挥保护作用。神经内分泌（NE）细胞是上皮细胞，具有神经元的许多特征，包括分泌囊泡的存在和感知环境刺激的能力。孤立性气道NE细胞的正常生理功能仍然是个谜。我们发现小鼠和人类气道基底干细胞能够感知缺氧。缺氧触发这些干细胞直接分化为孤立的NE细胞。缺氧期间这些孤立的 NE 细胞的消融会导致上皮损伤增加，而 NE 细胞肽 CGRP 的施用可以挽救这种过度损伤。因此，我们鉴定出能够直接感知缺氧并通过分化成单独的NE细胞来做出反应的干细胞，这些NE细胞分泌一种可以减轻缺氧损伤的保护肽。