{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:39:57Z","timestamp":1790343597760,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":617,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["F32HL149290-01"],"award-info":[{"award-number":["F32HL149290-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL141380"],"award-info":[{"award-number":["R01HL141380"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Lung Foundation Netherlands","award":["5.1.17.166"],"award-info":[{"award-number":["5.1.17.166"]}]},{"name":"The Lung Foundation Netherlands","award":["6.1.14.009"],"award-info":[{"award-number":["6.1.14.009"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["F32HL149290\u201001"],"award-info":[{"award-number":["F32HL149290\u201001"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL141380"],"award-info":[{"award-number":["R01HL141380"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Wnt\/\u03b2-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt\/\u03b2-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt\/\u03b2-catenin responsive progenitor cells and the potential impact of Wnt\/\u03b2-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\/\u03b2-catenin signaling in lung organoid formation. We identified an organoid-forming adult distal lung epithelial progenitor cell population characterized by a low Wnt\/\u03b2-catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. Endogenous Wnt\/\u03b2-catenin activity was required for the initiation of multiple subtypes of distal lung organoids derived from the Wntlow epithelial progenitors. Further ectopic Wnt\/\u03b2-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\/\u03b2-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\/\u03b2-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.<\/jats:p>\n                  <jats:sec>\n                    <jats:title\/>\n                  <\/jats:sec>","DOI":"10.1002\/stem.3241","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T15:09:40Z","timestamp":1591888180000},"page":"1467-1478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Wnt\/\u03b2-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema"],"prefix":"10.1093","volume":"38","author":[{"given":"Yan","family":"Hu","sequence":"first","affiliation":[{"name":"1 Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John-Poul","family":"Ng-Blichfeldt","sequence":"additional","affiliation":[{"name":"2 Lung Repair and Regeneration Unit, Helmholtz-Zentrum Munich, Ludwig-Maximilians-University, University Hospital Grosshadern, Member of the German Center of Lung Research (DZL), Munich, Germany"},{"name":"3 MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Ota","sequence":"additional","affiliation":[{"name":"2 Lung Repair and Regeneration Unit, Helmholtz-Zentrum Munich, Ludwig-Maximilians-University, University Hospital Grosshadern, Member of the German Center of Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ciminieri","sequence":"additional","affiliation":[{"name":"1 Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA"},{"name":"4 Department of Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Ren","sequence":"additional","affiliation":[{"name":"1 Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter S.","family":"Hiemstra","sequence":"additional","affiliation":[{"name":"5 Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stolk","sequence":"additional","affiliation":[{"name":"5 Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinoud","family":"Gosens","sequence":"additional","affiliation":[{"name":"4 Department of Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9414-5128","authenticated-orcid":false,"given":"Melanie","family":"K\u00f6nigshoff","sequence":"additional","affiliation":[{"name":"1 Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA"},{"name":"2 Lung Repair and Regeneration Unit, Helmholtz-Zentrum Munich, Ludwig-Maximilians-University, University Hospital Grosshadern, Member of the German Center of Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"2022022511412167200_stem3241-bib-0001","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0002-9440(10)64169-7","article-title":"Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction","volume":"161","author":"Giangreco","year":"2002","journal-title":"Am J Pathol"},{"key":"2022022511412167200_stem3241-bib-0002","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.stem.2009.04.002","article-title":"The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium","volume":"4","author":"Rawlins","year":"2009","journal-title":"Cell Stem Cell"},{"key":"2022022511412167200_stem3241-bib-0003","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1172\/JCI68782","article-title":"Type 2 alveolar cells 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