National Heart and Lung Institute, Imperial College London, London, UK.
Facility for Imaging by Light Microscopy, NHLI, Faculty of Medicine, Imperial College London, London, UK.
Nat Commun. 2019 Mar 12;10(1):1178. doi: 10.1038/s41467-019-09067-3.
Damage to alveoli, the gas-exchanging region of the lungs, is a component of many chronic and acute lung diseases. In addition, insufficient generation of alveoli results in bronchopulmonary dysplasia, a disease of prematurity. Therefore visualising the process of alveolar development (alveologenesis) is critical for our understanding of lung homeostasis and for the development of treatments to repair and regenerate lung tissue. Here we show live alveologenesis, using long-term, time-lapse imaging of precision-cut lung slices. We reveal that during this process, epithelial cells are highly mobile and we identify specific cell behaviours that contribute to alveologenesis: cell clustering, hollowing and cell extension. Using the cytoskeleton inhibitors blebbistatin and cytochalasin D, we show that cell migration is a key driver of alveologenesis. This study reveals important novel information about lung biology and provides a new system in which to manipulate alveologenesis genetically and pharmacologically.
肺泡损伤是许多慢性和急性肺部疾病的组成部分。此外，肺泡生成不足会导致支气管肺发育不良，这是一种早产儿疾病。因此，观察肺泡发育（肺泡发生）的过程对于我们理解肺稳态以及开发修复和再生肺组织的治疗方法至关重要。在这里，我们使用精密切割肺切片的长期延时成像来显示活的肺泡发生。我们揭示了在此过程中，上皮细胞具有高度的移动性，并且我们确定了有助于肺泡发生的特定细胞行为：细胞聚类、空心化和细胞延伸。使用细胞骨架抑制剂 blebbistatin 和细胞松弛素 D，我们表明细胞迁移是肺泡发生的关键驱动因素。这项研究揭示了有关肺生物学的重要新信息，并提供了一个新的系统，可以在该系统中遗传和药理学上操纵肺泡发生。
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