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Adv."],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>\n                    Pleuroparenchymal fibroelastosis (PPFE) is a progressive interstitial lung disease (ILD) with defining histology of intra-alveolar fibrosis with septal elastosis (AFE), suggesting unique cellular disease processes. Here, we present a binational single-nucleus RNA sequencing atlas of PPFE, based on explanted lungs from 40 patients. Immunofluorescence microscopy, RNA in situ hybridization, micro\u2013computed tomography (CT), and hierarchical phase-contrast (HiP) synchrotron CT provided spatial context. We identify PPFE-associated adventitial and elastofibrotic fibroblasts as key drivers of elastotic remodeling within an inflammatory microenvironment, maintained by immune cells forming tertiary lymphoid structures. Spatial mapping reveals an intriguing zonation of AFE, maintained by intercellular circuits between PPFE-associated cell types. Comparative analysis with idiopathic pulmonary fibrosis highlights\n                    <jats:italic toggle=\"yes\">CTHRC1<\/jats:italic>\n                    + fibrotic fibroblasts and aberrant basaloid cells as conserved profibrotic cellular machinery mediating collagen deposition across ILDs. This integrative atlas defines the cellular landscape of PPFE and dissects elastotic from fibrotic remodeling, providing a molecular rationale for niche-specific therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb5967","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:53:19Z","timestamp":1778579599000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["The pleuroparenchymal fibroelastosis atlas reveals aberrant cell states and their zonation as an alternate roadmap to lung fibrosis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1654-6668","authenticated-orcid":true,"given":"Jannik","family":"Ruwisch","sequence":"first","affiliation":[{"name":"Clinic for Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany."},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany."},{"name":"PRACTIS Clinician Scientist Program, Dean\u2019s Office for Academic Career Development, Hannover Medical School, Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7172-9101","authenticated-orcid":true,"given":"Aur\u00e9lie","family":"Cazes","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Pathologie, H\u00f4pital Bichat-Claude Bernard, AP-HP and Universit\u00e9 Paris Cit\u00e9, INSERM U1149, CRI, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4897-1064","authenticated-orcid":true,"given":"Lena M.","family":"Leiber","sequence":"additional","affiliation":[{"name":"Clinic for Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany."},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-0024","authenticated-orcid":true,"given":"Rapha\u00ebl","family":"Borie","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, Allergologie et Transplantation, AP-HP, H\u00f4pital Bichat, F-75018 Paris, France."},{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR 1149, Centre de Recherche de l\u2019Inflammation, F-75018 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Neubert","sequence":"additional","affiliation":[{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany."},{"name":"Institute of Pathology, Hannover Medical School, Hannover, 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