Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour

Khondoker M. Akram, Laura L. Yates, Róisín Mongey, Stephen Rothery, David C. A. Gaboriau, Jeremy Sanderson, Matthew Hind, Mark Griffiths and Charlotte H. Dean ()
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Khondoker M. Akram: Imperial College London
Laura L. Yates: Imperial College London
Róisín Mongey: Imperial College London
Stephen Rothery: Imperial College London
David C. A. Gaboriau: Imperial College London
Jeremy Sanderson: Harwell Campus
Matthew Hind: Imperial College London
Mark Griffiths: Imperial College London
Charlotte H. Dean: Imperial College London

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09067-3

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