{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:20:13Z","timestamp":1791292813013,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NICHD 2PO1HD068250"],"award-info":[{"award-number":["NICHD 2PO1HD068250"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21AI156597"],"award-info":[{"award-number":["R21AI156597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NICHD 2PO1HD068250"],"award-info":[{"award-number":["NICHD 2PO1HD068250"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21AI156597"],"award-info":[{"award-number":["R21AI156597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a robust methodology of epithelial progenitor derivation from tracheal aspirates of newborns. Basal stem cells (BSCs) from patients with CDH and preterm and term non-CDH control subjects were derived and analyzed by bulk RNA sequencing, assay for transposase accessible chromatin with sequencing, and air\u2013liquid interface differentiation. Lung sections from fetal human CDH samples and the nitrofen rat model of CDH were subjected to histological assessment of epithelial defects. Therapeutics to restore epithelial differentiation were evaluated in human epithelial cell culture and the nitrofen rat model of CDH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Transcriptomic and epigenetic profiling of CDH and control BSCs reveals a proinflammatory signature that is manifested by hyperactive nuclear factor kappa B and independent of severity and hernia size. In addition, CDH BSCs exhibit defective epithelial differentiation in vitro that recapitulates epithelial phenotypes found in fetal human CDH lung samples and fetal tracheas of the nitrofen rat model of CDH. Furthermore, blockade of nuclear factor kappa B hyperactivity normalizes epithelial differentiation phenotypes of human CDH BSCs in vitro and in nitrofen rat tracheas in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings have identified an underlying proinflammatory signature and BSC differentiation defects as a potential therapeutic target for airway epithelial defects in CDH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202205-0953oc","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T16:54:45Z","timestamp":1675356885000},"page":"1214-1226","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":30,"title":["A Tracheal Aspirate-derived Airway Basal Cell Model Reveals a Proinflammatory Epithelial Defect in Congenital Diaphragmatic Hernia"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-2619","authenticated-orcid":false,"given":"Richard","family":"Wagner","sequence":"first","affiliation":[{"name":"Division of Newborn Medicine and"},{"name":"Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Pediatric Surgery, University Hospital Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-7131","authenticated-orcid":false,"given":"Gaurang M.","family":"Amonkar","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine and"},{"name":"Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E.","family":"Shui","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamakshi","family":"Bankoti","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Hei","family":"Tse","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pediatrics & Child Health, Physiology & Pathophysiology, University of Manitoba and Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances A.","family":"High","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Surgery and"},{"name":"Division of Medical Genetics, Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Zalieckas","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry L.","family":"Buchmiller","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Department of Surgery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Zani","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Keijzer","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pediatrics & Child Health, Physiology & Pathophysiology, University of Manitoba and Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia K.","family":"Donahoe","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H.","family":"Lerou","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingbin","family":"Ai","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,1]]},"reference":[{"key":"2026012204462453200_bib1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/bjs.1800580507","article-title":"Lung hypoplasia in congenital diaphragmatic hernia. 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