Human distal airways contain a multipotent secretory cell that can regenerate alveoli.
Human distal airways contain a multipotent secretory cell that can regenerate alveoli.
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DOI：
10.1038/s41586-022-04552-0
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发表时间：
2022-04
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
人肺与其小鼠肺有很大不同，导致慢性阻塞性肺疾病中受疾病病理影响的独特远端气道结构。在人类中，气道的远端分支与肺泡气体交换龛交织，形成称为呼吸性细支气管的解剖结构。由于在小鼠中缺乏对应物，因此在人肺中控制呼吸性细支气管的细胞和分子机制仍然没有表征。在这里，我们表明，人类呼吸性细支气管包含一个独特的分泌细胞群，是不同的细胞在较大的近端气道。类器官模型显示，这些呼吸道分泌（RAS）细胞作为单向祖细胞的肺泡2型细胞，这是必不可少的维持和再生的肺泡生态位。RAS细胞谱系分化为肺泡2型细胞受Notch和Wnt信号传导调节。在慢性阻塞性肺疾病中，RAS细胞在转录上发生改变，对应于异常的肺泡2型细胞状态，这与人类和雪貂的吸烟暴露有关。这些数据确定了人类肺部区域中的一种独特祖细胞，该祖细胞在小鼠中没有发现，它在维持气体交换室方面发挥着关键作用，并在慢性肺病中发生改变。
The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.
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影响因子：
21.3
作者：
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158.5
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影响因子：
48
作者：
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Hemberg, Martin