{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:42:59Z","timestamp":1790188979437,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Disruption of normal pulmonary development is a leading cause of morbidity and mortality in infants. Congenital lung malformations are a unique model to study the molecular pathogenesis of isolated structural birth defects, as they are often surgically resected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To provide insight into the molecular pathogenesis of congenital lung malformations through analysis of cell-type and gene expression changes in these lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data, and lung tissue for DNA, RNA, and histology, were obtained from 58 infants undergoing surgical resection of a congenital lung lesion. Transcriptome-wide gene expression analysis was performed on paired affected and unaffected samples from a subset of infants (n\u2009=\u200914). A three-dimensional organoid culture model was used to assess isolated congenital lung malformation epithelium (n\u2009=\u20093).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Congenital lung lesions express higher levels of airway epithelial related genes, and dysregulated expression of genes related to the Ras and PI3K\u2013AKT\u2013mTOR (phosphatidylinositol 3-kinase\u2013AKT\u2013mammalian target of rapamycin) signaling pathways. Immunofluorescence confirmed differentiated airway epithelial cell types throughout all major subtypes of congenital lung lesions, and three-dimensional cell culture demonstrated a cell-autonomous defect in the epithelium of these lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides the first comprehensive analysis of the congenital lung malformation transcriptome and suggests that disruptions in Ras or PI3K\u2013AKT\u2013mTOR signaling may contribute to the pathology through an epithelial cell-autonomous defect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201706-1243oc","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T16:14:18Z","timestamp":1515773658000},"page":"1328-1339","source":"Crossref","is-referenced-by-count":55,"title":["Novel Molecular and Phenotypic Insights into Congenital Lung Malformations"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-0442","authenticated-orcid":false,"given":"Daniel T.","family":"Swarr","sequence":"first","affiliation":[{"name":"Division of Neonatology and Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Peranteau","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Pogoriler","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania; and"},{"name":"Department of Pediatrics"},{"name":"Penn Center for Pulmonary Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Scott","family":"Adzick","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly L.","family":"Hedrick","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Morley","sequence":"additional","affiliation":[{"name":"Penn Center for Pulmonary Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Zhou","sequence":"additional","affiliation":[{"name":"Penn Center for Pulmonary Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Morrisey","sequence":"additional","affiliation":[{"name":"Penn Center for Pulmonary Biology, and"},{"name":"Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, 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