Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis
Praveen Weeratunga,
Bethany Hunter,
Martin Sergeant,
Joshua Bull,
Colin Clelland,
Laura Denney,
Chaitanya Vuppusetty,
Rachel Burgoyne,
Jeongmin Woo,
Tian Hu,
Lee Borthwick,
James Shaw,
Agne Antanaviciute,
Andrew Filby,
Helen Byrne,
Andrew Fisher and
Ling-Pei Ho ()
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Praveen Weeratunga: 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
Tian Hu: University of Oxford
Lee Borthwick: Newcastle University Biosciences Institute
James Shaw: University of Newcastle
Agne Antanaviciute: University of Oxford
Andrew Filby: Newcastle University Biosciences Institute
Helen Byrne: University of Oxford
Andrew Fisher: University of Newcastle
Ling-Pei Ho: University of Oxford
Nature Communications, 2025, vol. 16, issue 1, 1-17
Abstract:
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.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61880-1
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DOI: 10.1038/s41467-025-61880-1
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