Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6

Area of Science:

• Pulmonary Biology
• Stem Cell Biology
• Regenerative Medicine

Background:

• The specific mesenchymal cell populations in the lung that regulate epithelial homeostasis and regeneration remain largely uncharacterized.
• Understanding these interactions is critical for developing therapies for lung diseases.

Purpose of the Study:

• To identify and characterize novel mesenchymal cell populations in the adult lung.
• To elucidate the roles of these cells in epithelial maintenance and repair.

Main Methods:

• Genetic lineage tracing in mice.
• Single-cell RNA sequencing (scRNA-seq).
• Organoid culture models.

Main Results:

• Lgr5 and Lgr6, typically stem cell markers, identify distinct mesenchymal cell subpopulations in the lung.
• Lgr6+ cells are airway-associated smooth muscle cells that promote airway epithelial differentiation via Wnt-Fgf10 signaling.
• Lgr5+ cells reside in alveolar regions and drive alveolar epithelial differentiation through Wnt activation.
• Ablation of Lgr6+ cells impairs in vivo airway injury repair.

Conclusions:

• Lgr5 and Lgr6 mark functionally distinct mesenchymal cells crucial for lung epithelial homeostasis and regeneration.
• Region-specific mesenchymal-epithelial crosstalk, mediated by Wnt signaling, governs lung tissue maintenance.
• These findings reveal new cellular players and mechanisms in lung repair and regeneration.