小柯机器人

美国宾夕法尼亚大学Edward E. Morrisey研究组发现人类远端气道含有一种可再生为肺泡的多能分泌细胞。相关论文发表在2022年3月30日出版的《自然》杂志上。

研究人员发现人类呼吸性细支气管中含有独特的分泌细胞群，不同于较大近端气道中的细胞。类器官模型表明，这些呼吸道分泌(RAS)细胞充当肺泡2型细胞的单向祖细胞，这对于肺泡生态位的维持和再生至关重要。RAS细胞谱系分化为2型肺泡细胞受Notch和Wnt信号通路的调节。在慢性阻塞性肺病中，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，这与人类和雪貂暴露于吸烟环境有关。这些数据确定了人肺中存在一个独特的祖细胞亚群，该祖细胞尚未在小鼠中发现，它在气体交换室维持中起关键作用，并且在慢性肺病个体中发生了改变。

据悉，人肺与其小鼠肺有很大不同，导致在慢性阻塞性肺病中远端气道结构明显受到疾病病理学的影响。在人体中，气道远端分支与肺泡气体交换生态位交织在一起，形成了呼吸细支气管结构。由于在小鼠中缺乏对应物，控制人肺中呼吸性细支气管的细胞和分子机制仍然未知。

附：英文原文

Title: Human distal airways contain a multipotent secretory cell that can regenerate alveoli

Author: Basil, Maria C., Cardenas-Diaz, Fabian L., Kathiriya, Jaymin J., Morley, Michael P., Carl, Justine, Brumwell, Alexis N., Katzen, Jeremy, Slovik, Katherine J., Babu, Apoorva, Zhou, Su, Kremp, Madison M., McCauley, Katherine B., Li, Shanru, Planer, Joseph D., Hussain, Shah S., Liu, Xiaoming, Windmueller, Rebecca, Ying, Yun, Stewart, Kathleen M., Oyster, Michelle, Christie, Jason D., Diamond, Joshua M., Engelhardt, John F., Cantu, Edward, Rowe, Steven M., Kotton, Darrell N., Chapman, Harold A., Morrisey, Edward E.

Issue&Volume: 2022-03-30

Abstract: 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. Human respiratory bronchioles contain a unique population of secretory cells called respiratory airway secretory cells that are distinct from the cells in the larger proximal airways, and act as unidirectional progenitors for alveolar type 2 cells.

DOI: 10.1038/s41586-022-04552-0

Source: https://www.nature.com/articles/s41586-022-04552-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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