biostudies-literaturePolkoff KMNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of Health Office of the DirectorNIAMS NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSNIH HHS496-509https://www.ebi.ac.uk/biostudies/studies/S-EPMC12051919biostudies-literatureUnknown72(5)Cells expressing leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) play a pivotal role in homeostasis, repair, and regeneration in multiple organs, including skin and gastrointestinal tract, but little is known about their role in the lung. Findings from mice, a widely used animal model, suggest that lung LGR5 expression differs from that of humans. In this work, using a new transgenic pig model, we identify two main populations of LGR5⁺ cells in the lung that are conserved in human but not mouse lungs. Using RNA sequencing, three-dimensional imaging, and organoid models, we determine that in the fetal lung, epithelial LGR5 expression is transient in a subpopulation of SOX9⁺/ETV5⁺/SFTPC⁺ progenitor lung tip cells. In contrast, epAmerican journal of respiratory cell and molecular biologyNovel Porcine Model Reveals Two Distinct LGR5 Cell Types during Lung Development and Homeostasis.PMC12051919R21 OD019738T34GM131947F31AR077423F31 AR077423T34 GM131947R21OD019738P30 DK034987P30DK034987Gleason KMoatti AMurphy YMurthy PKTata PRLampe RCarter APiedrahita JAEdwards LChung JSimon JMGupta NKGreenbaum APolkoff KMTata AfalseNovel Porcine Model Reveals Two Distinct LGR5 Cell Types during Lung Development and Homeostasis.Cells expressing leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) play a pivotal role in homeostasis, repair, and regeneration in multiple organs, including skin and gastrointestinal tract, but little is known about their role in the lung. Findings from mice, a widely used animal model, suggest that lung LGR5 expression differs from that of humans. In this work, using a new transgenic pig model, we identify two main populations of LGR5⁺ cells in the lung that are conserved in human but not mouse lungs. Using RNA sequencing, three-dimensional imaging, and organoid models, we determine that in the fetal lung, epithelial LGR5 expression is transient in a subpopulation of SOX9⁺/ETV5⁺/SFTPC⁺ progenitor lung tip cells. In contrast, ep2025-01-01T00:00:00Z2025 May2026-06-05T11:49:34.71Z2026-05-16T03:13:34.239ZS-EPMC120519193949985010.1165/rcmb.2024-0040OC10.1165/rcmb.2024-0040oc