{"doi":"10.1002/stem.3241","title":"Wnt/β-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema","abstract":"Abstract Wnt/β-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/β-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt/β-catenin responsive progenitor cells and the potential impact of Wnt/β-catenin signaling on adult distal lung epithelial progenitor cell function in emphysema are poorly understood. Here, we used TCF/Lef:H2B/GFP reporter mice to investigate the role of Wnt/β-catenin signaling in lung organoid formation. We identified an organoid-forming adult distal lung epithelial progenitor cell population characterized by a low Wnt/β-catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. Endogenous Wnt/β-catenin activity was required for the initiation of multiple subtypes of distal lung organoids derived from the Wntlow epithelial progenitors. Further ectopic Wnt/β-catenin activation specifically led to an increase in alveolar organoid number; however, the subsequent proliferation of alveolar epithelial cells in the organoids did not require constitutive Wnt/β-catenin signaling. Distal lung epithelial progenitor cells derived from the mouse model of elastase-induced emphysema exhibited reduced organoid forming capacity. This was rescued by Wnt/β-catenin signal activation, which largely increased the number of alveolar organoids. Together, our study reveals a novel mechanism of lung epithelial progenitor cell activation in homeostasis and emphysema.","journal":"Stem Cells","year":2020,"id":59406,"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":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":312372,"name":"John-Poul Ng-Blichfeldt","orcid":"0000-0002-8332-2659","position":1,"is_corresponding":false},{"id":312373,"name":"Chiharu Ota","orcid":"0000-0002-0644-1144","position":2,"is_corresponding":false},{"id":541,"name":"Chiara Ciminieri","orcid":"0000-0002-4689-7648","position":3,"is_corresponding":false},{"id":312374,"name":"Wenhua Ren","orcid":"0000-0002-8429-5963","position":4,"is_corresponding":false},{"id":2959,"name":"Pieter S. Hiemstra","orcid":"0000-0002-0238-5982","position":5,"is_corresponding":false},{"id":312375,"name":"Jan Stolk","orcid":"0000-0002-7887-386X","position":6,"is_corresponding":false},{"id":560,"name":"Reinoud Gosens","orcid":"0000-0002-5595-152X","position":7,"is_corresponding":false},{"id":574,"name":"Melanie Königshoff","orcid":"0000-0001-9414-5128","position":8,"is_corresponding":false},{"id":534,"name":"Yan Hu","orcid":"0000-0003-0586-6527","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T21:07:59.189921Z","pmid":"32526076","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":[]}