{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:01:45Z","timestamp":1784642505465,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["KFO309 P7, SFB CRC1213-project A04 and EL 931\/4-1"],"award-info":[{"award-number":["KFO309 P7, SFB CRC1213-project A04 and EL 931\/4-1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bundes Ministerium f\u00fcr Bildung und Forschung","award":["RARE-ILD consortium (European Joint Program on Rare Diseases, EJP-RD)"],"award-info":[{"award-number":["RARE-ILD consortium (European Joint Program on Rare Diseases, EJP-RD)"]}]},{"name":"Lung Clinic Waldhof Elgershausen","award":["Lung Fibrosis Stipend"],"award-info":[{"award-number":["Lung Fibrosis Stipend"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates, in a reactive manner, all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by LysoTracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial LysoTracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s that behave in a compensatory manner during bleomycin injury and in the donor\/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expressed AEC2 and basal cell markers, resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of LysoTracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5, and CD24 expression in human lung epithelial cells. Combining functional analysis with extracellular and intracellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis.<\/jats:p>","DOI":"10.3390\/cells11020235","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-7799","authenticated-orcid":false,"given":"Roxana Maria","family":"Wasnick","sequence":"first","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Shalashova","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5544-9647","authenticated-orcid":false,"given":"Jochen","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Excellence Cluster Cardiopulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"},{"name":"Institute for Lung Health (ILH), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-7201","authenticated-orcid":false,"given":"Ali","family":"Khadim","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Institute for Lung Health (ILH), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Hackstein","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hecker","sequence":"additional","affiliation":[{"name":"Department of General and Thoracic Surgery, University Hospital Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Hoetzenecker","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-0894","authenticated-orcid":false,"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Excellence Cluster Cardiopulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"},{"name":"Institute for Lung Health (ILH), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Bellusci","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Excellence Cluster Cardiopulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"Institute for Lung Health (ILH), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7504-3417","authenticated-orcid":false,"given":"Elie","family":"El Agha","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Institute for Lung Health (ILH), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-2469","authenticated-orcid":false,"given":"Clemens","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Excellence Cluster Cardiopulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"European IPF Registry\/UGLMC Giessen Biobank, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Guenther","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany"},{"name":"Excellence Cluster Cardiopulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"Institute for Lung Health (ILH), 35392 Giessen, Germany"},{"name":"Department of General and Thoracic Surgery, University Hospital Giessen, 35392 Giessen, Germany"},{"name":"European IPF Registry\/UGLMC Giessen Biobank, 35392 Giessen, Germany"},{"name":"Lung Clinic Waldhof-Elgershausen, 35753 Greifenstein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1183\/09059180.00001012","article-title":"Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis","volume":"21","author":"Korfei","year":"2012","journal-title":"Eur. Respir. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"American thoracic society documents diagnosis of idiopathic pulmonary fibrosis an official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"198","author":"Raghu","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ccm.2011.12.001","article-title":"Idiopathic pulmonary fibrosis: Diagnosis and epidemiology","volume":"33","author":"Olson","year":"2012","journal-title":"Clin. Chest Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Shumar, J.N., Chandel, A., King, C.S., and Bendstrup, M. (2021). Clinical medicine antifibrotic therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD. J. Clin. Med., 10.","DOI":"10.3390\/jcm10112285"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Parimon, T., Hohmann, M.S., Yao, C., Marchioni, A., and Tonelli, R. (2021). Pathogenic mechanisms in lung fibrosis. Int. J. Mol. Sci., 2021.","DOI":"10.20944\/preprints202105.0427.v1"},{"key":"ref_6","first-page":"4","article-title":"Review series pulmonary brosis: Patterns and perpetrators","volume":"122","author":"Noble","year":"2012","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1164\/rccm.200810-1615OC","article-title":"Targeted injury of type ii alveolar epithelial cells induces pulmonary fibrosis","volume":"181","author":"Sisson","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1164\/rccm.202004-1274OC","article-title":"Senescence of alveolar type 2 cells drives progressive pulmonary fibrosis","volume":"203","author":"Yao","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2013.00173","article-title":"The epithelium in idiopathic pulmonary fibrosis: Breaking the barrier","volume":"4","author":"Camelo","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/nature12930","article-title":"Alveolar progenitor and stem cells in lung development, renewal and cancer","volume":"507","author":"Desai","year":"2014","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature25786","article-title":"Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor","volume":"555","author":"Zacharias","year":"2018","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1073\/pnas.95.4.1579","article-title":"Dynamics of surfactant release in alveolar type II Cells","volume":"95","author":"Haller","year":"1998","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0925-4439(98)00066-0","article-title":"Synthesis, processing and secretion of surfactant proteins B and C","volume":"1408","author":"Weaver","year":"1998","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8672","DOI":"10.1074\/jbc.275.12.8672","article-title":"Intracellular localization of processing events in human surfactant protein B biosynthesis","volume":"275","author":"Korimilli","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.molcel.2020.10.042","article-title":"Mechanism of lamellar body formation by lung surfactant protein, B","volume":"81","author":"Sever","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Strunz, M., Simon, L.M., Ansari, M., Mattner, L.F., Angelidis, I., Mayr, C.H., Kathiriya, J., Yee, M., Ogar, P., and Sengupta, A. (2019). Longitudinal single cell transcriptomics reveals Krt8+ alveolar epithelial progenitors in lung regeneration. bioRxiv.","DOI":"10.1101\/705244"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nature14112","article-title":"Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury","volume":"517","author":"Vaughan","year":"2015","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/nm.4192","article-title":"Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice","volume":"22","author":"Liang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"L1260","DOI":"10.1152\/ajplung.00065.2016","article-title":"Surfactant dysfunction during overexpression of TGF-\u03921 precedes profibrotic lung remodeling in vivo","volume":"310","author":"Boden","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41374-019-0189-x","article-title":"Surfactant dysfunction and alveolar collapse are linked with fibrotic septal wall remodeling in the TGF-\u03921-induced mouse model of pulmonary fibrosis","volume":"99","author":"Beike","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"L507","DOI":"10.1152\/ajplung.00139.2015","article-title":"Lost after translation: Insights from pulmonary surfactant for understanding the role of alveolar epithelial dysfunction and cellular quality control in fibrotic lung disease","volume":"309","author":"Mulugeta","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wasnick, R.M., Korfei, M., Piskulak, K., Henneke, I., Wilhelm, J., Mahavadi, P., von der Beck, D., Koch, M., Shalashova, I., and Klymenko, O. (2019). Restored alveolar epithelial differentiation and reversed human lung fibrosis upon notch inhibition. bioRxiv, 580498.","DOI":"10.1101\/580498"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2101100118","DOI":"10.1073\/pnas.2101100118","article-title":"Resetting Proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis","volume":"118","author":"Watanabe","year":"2021","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1172\/JCI57673","article-title":"Integrin A6\u03b24 identifies an adult distal lung epithelial population with regenerative potential in mice","volume":"121","author":"Chapman","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-66966-y","article-title":"Distal lung epithelial progenitor cell function declines with age","volume":"10","author":"Watson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1165\/rcmb.2016-0150OC","article-title":"Alternative progenitor lineages regenerate the adult lung depleted of alveolar epithelial type 2 cells","volume":"56","author":"Yee","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_27","first-page":"1","article-title":"Detection and quantification of epithelial progenitor cell populations in human healthy and IPF lungs","volume":"17","author":"Smirnova","year":"2016","journal-title":"Respri. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.90558","article-title":"Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis","volume":"1","author":"Xu","year":"2016","journal-title":"JCI Insight"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41586-020-2922-4","article-title":"A molecular cell atlas of the human lung from single-cell RNA sequencing","volume":"587","author":"Travaglini","year":"2020","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1164\/rccm.201712-2410OC","article-title":"Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis","volume":"199","author":"Reyfman","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Adams, T.S., Schupp, J.C., Poli, S., Ayaub, E.A., Neumark, N., Ahangari, F., Chu, S.G., Raby, B.A., DeIuliis, G., and Januszyk, M. (2020). Single-Cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Sci. Adv., 6.","DOI":"10.1126\/sciadv.aba1983"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eaba1972","DOI":"10.1126\/sciadv.aba1972","article-title":"Single-Cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis","volume":"6","author":"Habermann","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131597","DOI":"10.1172\/jci.insight.131597","article-title":"Transcriptional regulatory model of fibrosis progression in the human lung","volume":"4","author":"McDonough","year":"2019","journal-title":"JCI Insight"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"American Thoracic Society (2000). Idiopathic Pulmonary Fibrosis: Diagnosis and Treatment International Consensus Statement. Am. J. Respir. Crit. Care Med., 161, 646\u2013664.","DOI":"10.1164\/ajrccm.161.2.ats3-00"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1634\/stemcells.2008-0838","article-title":"Prospective isolation of bronchiolar stem cells based upon immunophenotypic and autofluorescence characteristics","volume":"27","author":"Teisanu","year":"2009","journal-title":"Stem Cells"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1165\/rcmb.2010-0098OC","article-title":"Functional Analysis of Two Distinct Bronchiolar Progenitors during Lung Injury and Repair","volume":"44","author":"Teisanu","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1165\/rcmb.2019-0191ST","article-title":"American thoracic society documents improving the quality and reproducibility of flow cytometry in the lung an official american thoracic society workshop report","volume":"61","author":"Tighe","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_38","unstructured":"Smyth, G.K. (2005). Limma: Linear Models for Microarray Data, Springer."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: Open software development for computational biology and bioinformatics","volume":"5","author":"Gentleman","year":"2004","journal-title":"Genome Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1046-2023(03)00155-5","article-title":"Normalization of CDNA microarray data","volume":"31","author":"Smyth","year":"2003","journal-title":"Methods"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Smyth, G.K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol., 3.","DOI":"10.2202\/1544-6115.1027"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1465-9921-14-123","article-title":"LysoTracker is a marker of differentiated alveolar type II cells","volume":"14","author":"Bertoncello","year":"2013","journal-title":"Respir. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-17358-3","article-title":"Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis","volume":"11","author":"Strunz","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3109\/01902148.2014.979516","article-title":"The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis","volume":"41","author":"Williamson","year":"2015","journal-title":"Exp. Lung Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1369\/jhc.2010.956433","article-title":"HTII-280, a biomarker specific to the apical plasma membrane of human lung alveolar type II cells","volume":"58","author":"Gonzalez","year":"2010","journal-title":"J. Histochem. Cytochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1165\/rcmb.2018-0416TR","article-title":"The human lung cell atlas: A high-resolution reference map of the human lung in health and disease","volume":"61","author":"Schiller","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_47","first-page":"1","article-title":"Isolation and enrichment of human lung epithelial progenitor cells for organoid culture","volume":"2020","author":"Konda","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12771","DOI":"10.1073\/pnas.0906850106","article-title":"Basal cells as stem cells of the mouse trachea and human airway epithelium","volume":"106","author":"Rock","year":"2009","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fcell.2016.00146","article-title":"CD24: A rheostat that modulates cell surface receptor signaling of diverse receptors","volume":"4","author":"Ayre","year":"2016","journal-title":"Front. Cell Develop. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1158\/2159-8290.CD-20-1285","article-title":"Resolving the spatial and cellular architecture of lung adenocarcinoma by multiregion single-cell sequencing","volume":"11","author":"Sinjab","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41586-019-1456-0","article-title":"CD24 signalling through macrophage siglec-10 is a target for cancer immunotherapy","volume":"572","author":"Barkal","year":"2019","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature13173","article-title":"Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-Seq","volume":"509","author":"Treutlein","year":"2014","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/gene.20093","article-title":"Normal lung development and function after Sox9 inactivation in the respiratory epithelium","volume":"41","author":"Perl","year":"2005","journal-title":"Genesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E4456","DOI":"10.1073\/pnas.1311847110","article-title":"Sox9 plays multiple roles in the lung epithelium during branching morphogenesis","volume":"110","author":"Rockich","year":"2013","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"L144","DOI":"10.1152\/ajplung.00379.2017","article-title":"Human lung branching morphogenesis is orchestrated by the spatiotemporal distribution of ACTA2, SOX2, and SOX9","volume":"314","author":"Danopoulos","year":"2018","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.dib.2016.08.047","article-title":"Dataset of differentially expressed genes from SOX9 over-expressing NT2\/D1 cells","volume":"9","author":"Ludbrook","year":"2016","journal-title":"Data Brief"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.biocel.2016.08.005","article-title":"SOX9 regulates expression of the male fertility gene Ets Variant Factor 5 (ETV5) during mammalian sex development","volume":"79","author":"Alankarage","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1093\/hmg\/ddq558","article-title":"SOX9 controls epithelial branching by activating RET effector genes during kidney development","volume":"20","author":"Reginensi","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fgene.2019.00178","article-title":"Characterization of Tg(Etv4-GFP)and Etv5RFP reporter lines in the context of fibroblast growth factor 10 signaling during mouse embryonic lung development","volume":"10","author":"Jones","year":"2019","journal-title":"Front. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0012-1606(03)00359-2","article-title":"Role for ETS domain transcription factors Pea3\/Erm in mouse lung development","volume":"261","author":"Liu","year":"2003","journal-title":"Develop. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1073\/pnas.1621177114","article-title":"Transcription factor Etv5 is essential for the maintenance of alveolar type II cells","volume":"114","author":"Zhang","year":"2017","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2004168","DOI":"10.1183\/13993003.04168-2020","article-title":"Identification of a novel subset of alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy","volume":"58","author":"Ahmadvand","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1101\/gad.319418.118","article-title":"Repairing the lungs one breath at a time: How dedicated or facultative are you?","volume":"32","author":"Leach","year":"2018","journal-title":"Genes Dev."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/2\/235\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:28:20Z","timestamp":1760365700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/2\/235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["cells11020235"],"URL":"https:\/\/doi.org\/10.3390\/cells11020235","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202112.0033.v1","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,11]]}}}