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

Author

Listed:
  • 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
    National Institute for Health Research (NIHR) Respiratory Biomedical Research Unit at the Royal Brompton & Harefield NHS Foundation Trust and Imperial College)

  • Mark Griffiths

    (Imperial College London
    St Bartholomew’s Hospital)

  • Charlotte H. Dean

    (Imperial College London
    Harwell Campus)

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.

Suggested Citation

  • Khondoker M. Akram & Laura L. Yates & Róisín Mongey & Stephen Rothery & David C. A. Gaboriau & Jeremy Sanderson & Matthew Hind & Mark Griffiths & Charlotte H. Dean, 2019. "Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09067-3
    DOI: 10.1038/s41467-019-09067-3
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    Cited by:

    1. Elena Ortiz-Zapater & Dustin C. Bagley & Virginia Llopis Hernandez & Luke B. Roberts & Thomas J. A. Maguire & Felizia Voss & Philipp Mertins & Marieluise Kirchner & Isabel Peset-Martin & Grzegorz Wosz, 2022. "Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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