{"doi":"10.1165/rcmb.2024-0040oc","title":"Novel Porcine Model Reveals Two Distinct LGR5 Cell Types during Lung Development and Homeostasis","abstract":"Abstract 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, epithelial LGR5 expression is absent from postnatal lung but is reactivated in bronchioalveolar organoids derived from basal airway cells. We also describe a separate population of mesenchymal LGR5+ cells that surrounds developing and mature airways, lies adjacent to airway basal cells, and is closely associated with nerve fibers. Transcriptionally, mesenchymal LGR5+ cells include a subset of peribronchial fibroblasts that express unique patterns of SHH, FGF, WNT, and TGF-β signaling pathway genes. These results support distinct roles for LGR5+ cells in the lung and describe a physiologically relevant animal model for further studies on the function of these cells in repair and regeneration.","journal":"American Journal of Respiratory Cell and Molecular Biology","year":2024,"id":482088,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1322742,"name":"Ross Lampe","orcid":null,"position":1,"is_corresponding":false},{"id":872656,"name":"Nithin Gupta","orcid":"0000-0002-6696-8984","position":2,"is_corresponding":false},{"id":873316,"name":"Yanet Murphy","orcid":null,"position":3,"is_corresponding":false},{"id":530572,"name":"Jae-Wook Chung","orcid":"0000-0002-1055-2357","position":4,"is_corresponding":false},{"id":108318,"name":"Amber Carter","orcid":null,"position":5,"is_corresponding":false},{"id":11659,"name":"Jeremy M. Simon","orcid":"0000-0003-3906-1663","position":6,"is_corresponding":false},{"id":531210,"name":"Katherine Gleason","orcid":null,"position":7,"is_corresponding":false},{"id":677296,"name":"Adele Moatti","orcid":"0000-0002-6946-5370","position":8,"is_corresponding":false},{"id":12144,"name":"Preetish Kadur Lakshminarasimha Murthy","orcid":"0000-0002-9762-8376","position":9,"is_corresponding":false},{"id":1322410,"name":"Laura Edwards","orcid":"0000-0002-9133-9848","position":10,"is_corresponding":false},{"id":245908,"name":"Alon Greenbaum","orcid":"0000-0002-2897-876X","position":11,"is_corresponding":false},{"id":71961,"name":"Aleksandra Tata","orcid":"0000-0003-3270-0485","position":12,"is_corresponding":false},{"id":12178,"name":"Purushothama Rao Tata","orcid":"0000-0003-4837-0337","position":13,"is_corresponding":false},{"id":374580,"name":"Jorge A. Piedrahita","orcid":"0000-0001-9751-3192","position":14,"is_corresponding":false},{"id":530571,"name":"Kathryn M. Polkoff","orcid":"0000-0001-6227-622X","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:07:14.349221Z","pmid":"39499850","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}