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Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage

Author

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  • Maria Hurskainen

    (Ottawa Hospital Research Institute
    Helsinki University Hospital and University of Helsinki
    University of Helsinki and Helsinki University Hospital
    University of Ottawa)

  • Ivana Mižíková

    (Ottawa Hospital Research Institute
    University of Ottawa)

  • David P. Cook

    (University of Ottawa
    Ottawa Hospital Research Institute)

  • Noora Andersson

    (University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Chanèle Cyr-Depauw

    (Ottawa Hospital Research Institute
    University of Ottawa)

  • Flore Lesage

    (Ottawa Hospital Research Institute
    University of Ottawa)

  • Emmi Helle

    (Helsinki University Hospital and University of Helsinki
    University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Laurent Renesme

    (Ottawa Hospital Research Institute
    University of Ottawa)

  • Robert P. Jankov

    (University of Ottawa
    Children’s Hospital of Eastern Ontario (CHEO) and CHEO Research Institute, University of Ottawa
    Molecular Biomedicine Program, Children’s Hospital of Eastern Ontario Research Institute)

  • Markku Heikinheimo

    (University of Helsinki and Helsinki University Hospital)

  • Barbara C. Vanderhyden

    (University of Ottawa
    Ottawa Hospital Research Institute
    University of Ottawa/The Ottawa Hospital)

  • Bernard Thébaud

    (Ottawa Hospital Research Institute
    University of Ottawa
    Children’s Hospital of Eastern Ontario (CHEO) and CHEO Research Institute, University of Ottawa)

Abstract

During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia with validation of some of the findings in lungs from BPD patients. We observe dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, stromal fibroblasts, capillary endothelium and macrophage populations. Pathway analysis and predicted dynamic cellular crosstalk suggest inflammatory signaling as the main driver of hyperoxia-induced changes. Our data provides a single-cell view of cellular changes associated with late lung development in health and disease.

Suggested Citation

  • Maria Hurskainen & Ivana Mižíková & David P. Cook & Noora Andersson & Chanèle Cyr-Depauw & Flore Lesage & Emmi Helle & Laurent Renesme & Robert P. Jankov & Markku Heikinheimo & Barbara C. Vanderhyden , 2021. "Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21865-2
    DOI: 10.1038/s41467-021-21865-2
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    Cited by:

    1. Leila R. Martins & Lina Sieverling & Michelle Michelhans & Chiara Schiller & Cihan Erkut & Thomas G. P. Grünewald & Sergio Triana & Stefan Fröhling & Lars Velten & Hanno Glimm & Claudia Scholl, 2024. "Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Igor O. Shmarakov & Galina A. Gusarova & Mohammad N. Islam & María Marhuenda-Muñoz & Jahar Bhattacharya & William S. Blaner, 2023. "Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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