2. Academic Validation
  3. An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung

An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung

  • Science. 2024 Dec 13;386(6727):eado5561. doi: 10.1126/science.ado5561.
Dakota L Jones 1 2,  Michael P Morley 1 2 3,  Xinyuan Li 4,  Yun Ying 1 2,  Gan Zhao 1 2,  Sarah E Schaefer 1 2,  Luis R Rodriguez 1 2,  Fabian L Cardenas-Diaz 1 2,  Shanru Li 1 2,  Su Zhou 1 2,  Ullas V Chembazhi 1 2,  Mijeong Kim 1 2,  Chen Shen 1 2,  Ana Nottingham 1 2,  Susan M Lin 1 2,  Edward Cantu 4,  Joshua M Diamond 1,  Maria C Basil 1 2 3,  Andrew E Vaughan 5,  Edward E Morrisey 1 2 3 6
Affiliations

Affiliations

  • 1 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 2 Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 3 Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
  • 4 Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 5 Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 6 Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
PMID: 39666855 DOI: 10.1126/science.ado5561
Abstract

Severe lung injury causes airway basal stem cells to migrate and outcompete alveolar stem cells, resulting in dysplastic repair. We found that this "stem cell collision" generates an injury-induced tissue niche containing keratin 5+ epithelial cells and plastic Pdgfra+ mesenchymal cells. Single-cell analysis revealed that the injury-induced niche is governed by mesenchymal proliferation and Notch signaling, which suppressed Wnt/Fgf signaling in the injured niche. Conversely, loss of Notch signaling rewired alveolar signaling patterns to promote functional regeneration and gas exchange. Signaling patterns in injury-induced niches can differentiate fibrotic from degenerative human lung diseases through altering the direction of Wnt/Fgf signaling. Thus, we have identified an injury-induced niche in the lung with the ability to discriminate human lung disease phenotypes.

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