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Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis

Author

Listed:
  • Praveen Weeratunga

    (University of Oxford
    University of Oxford)

  • Bethany Hunter

    (Newcastle University Biosciences Institute)

  • Martin Sergeant

    (University of Oxford)

  • Joshua Bull

    (University of Oxford)

  • Colin Clelland

    (Weill Cornell Medical College)

  • Laura Denney

    (University of Oxford)

  • Chaitanya Vuppusetty

    (University of Oxford)

  • Rachel Burgoyne

    (Newcastle University Biosciences Institute)

  • Jeongmin Woo

    (University of Oxford
    University of Oxford)

  • Tian Hu

    (University of Oxford
    University of Oxford)

  • Lee Borthwick

    (Newcastle University Biosciences Institute)

  • James Shaw

    (University of Newcastle
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

  • Agne Antanaviciute

    (University of Oxford
    University of Oxford)

  • Andrew Filby

    (Newcastle University Biosciences Institute)

  • Helen Byrne

    (University of Oxford
    University of Oxford)

  • Andrew Fisher

    (University of Newcastle
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

  • Ling-Pei Ho

    (University of Oxford
    University of Oxford)

Abstract

Healthy alveolar repair relies on the ability of alveolar stem cells to differentiate into specialized epithelial cells for gas exchange. In chronic fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF), this regenerative process is abnormal but the underlying mechanisms remain unclear. Here, using human lung tissue that represents different stages of disease and a 33-plex single-cell imaging mass cytometry (IMC), we present a high-resolution, temporo-spatial cell atlas of the regenerating alveolar niche. With unbiased mathematical methods which quantify statistically enriched interactions, CD206himacrophage subtype and an alveolar basal intermediate epithelial cell emerge as the most statistically robust spatial association in the epithelial and immune cell interactome, found across all stages of disease. Spatially resolved receptor–ligand analysis further offers an in silico mechanism by which these macrophages may influence epithelial regeneration. These findings provide a foundational step toward understanding immune–epithelial dynamics in aberrant alveolar regeneration in IPF.

Suggested Citation

  • Praveen Weeratunga & Bethany Hunter & Martin Sergeant & Joshua Bull & Colin Clelland & Laura Denney & Chaitanya Vuppusetty & Rachel Burgoyne & Jeongmin Woo & Tian Hu & Lee Borthwick & James Shaw & Agn, 2025. "Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61880-1
    DOI: 10.1038/s41467-025-61880-1
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