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Related Experiment Video

Updated: Jun 8, 2025

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Novel Porcine Model Reveals Two Distinct LGR5 Cell Types during Lung Development and Homeostasis.

Kathryn M Polkoff1,2, Ross Lampe1,2, Nithin K Gupta2,3

  • 1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, and.

American Journal of Respiratory Cell and Molecular Biology
|November 5, 2024
PubMed
Summary

Researchers identified two lung cell populations expressing leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) in pigs, conserved in humans but not mice. These LGR5+ cells have distinct roles in lung development and regeneration.

Keywords:
LGR5lung developmentnerve-associated fibroblastspig model

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Area of Science:

  • Pulmonology
  • Cell Biology
  • Regenerative Medicine

Background:

  • Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) expressing cells are crucial for tissue homeostasis and repair in various organs.
  • The role and expression of LGR5+ cells in the lung are poorly understood, with known differences between human and mouse models.
  • A novel transgenic pig model offers a potential avenue to study lung LGR5+ cells in a more human-relevant context.

Purpose of the Study:

  • To identify and characterize LGR5-expressing cell populations in the lung.
  • To investigate the developmental and spatial distribution of these cells.
  • To explore the potential roles of LGR5+ cells in lung repair and regeneration using a new animal model.

Main Methods:

  • Utilized a transgenic pig model to study lung LGR5 expression.
  • Employed RNA sequencing, three-dimensional imaging, and organoid models for detailed analysis.
  • Characterized both epithelial and mesenchymal LGR5+ cell populations and their transcriptional profiles.

Main Results:

  • Identified two distinct LGR5+ cell populations in pig lungs, conserved in humans but absent in mice.
  • Discovered transient epithelial LGR5 expression in fetal lung progenitors (SOX9+/ETV5+/SFTPC+) and its reactivation in postnatal basal airway cells via organoids.
  • Characterized mesenchymal LGR5+ cells surrounding airways, associated with nerves, and identified a subset of peribronchial fibroblasts with unique signaling gene expression (SHH, FGF, WNT, TGF-β).

Conclusions:

  • LGR5+ cells exhibit distinct epithelial and mesenchymal populations in the lung with species-specific expression patterns.
  • These findings highlight the importance of the pig model for studying human lung biology.
  • LGR5+ cells, particularly mesenchymal subtypes, are implicated in lung development and may play significant roles in airway repair and regeneration.