{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:01:31Z","timestamp":1789387291349,"version":"build-2803163510"},"reference-count":123,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009480","name":"Stichting Vrienden van het Sophia","doi-asserted-by":"publisher","award":["493"],"award-info":[{"award-number":["493"]}],"id":[{"id":"10.13039\/501100009480","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009480","name":"Stichting Vrienden van het Sophia","doi-asserted-by":"publisher","award":["436"],"award-info":[{"award-number":["436"]}],"id":[{"id":"10.13039\/501100009480","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009480","name":"Stichting Vrienden van het Sophia","doi-asserted-by":"publisher","award":["S13-09"],"award-info":[{"award-number":["S13-09"]}],"id":[{"id":"10.13039\/501100009480","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edgar Doncker Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are relatively frequently occurring foregut malformations. EA\/TEF is thought to have a strong genetic component. Not much is known regarding the biological processes disturbed or which cell type is affected in patients. This hampers the detection of the responsible culprits (genetic or environmental) for the origin of these congenital anatomical malformations. Therefore, we examined gene expression patterns in the TEF and compared them to the patterns in esophageal, tracheal and lung control samples. We studied tissue organization and key proteins using immunohistochemistry. There were clear differences between TEF and control samples. Based on the number of differentially expressed genes as well as histological characteristics, TEFs were most similar to normal esophagus. The BMP-signaling pathway, actin cytoskeleton and extracellular matrix pathways are downregulated in TEF. Genes involved in smooth muscle contraction are overexpressed in TEF compared to esophagus as well as trachea. These enriched pathways indicate myofibroblast activated fibrosis. TEF represents a specific tissue type with large contributions of intestinal smooth muscle cells and neurons. All major cell types present in esophagus are present\u2014albeit often structurally disorganized\u2014in TEF, indicating that its etiology should not be sought in cell fate specification.<\/jats:p>","DOI":"10.1371\/journal.pone.0242167","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T18:31:08Z","timestamp":1605637868000},"page":"e0242167","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Histological, immunohistochemical and transcriptomic characterization of human tracheoesophageal fistulas"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-4010","authenticated-orcid":true,"given":"Erwin","family":"Brosens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine F.","family":"Felix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Boerema-de Munck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-3796","authenticated-orcid":true,"given":"Elisabeth M.","family":"Lodder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Swagemakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjon","family":"Buscop-van Kempen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald R.","family":"de Krijger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene M. 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