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Disruption of the compartmentalization process leads to esophageal atresia\/tracheoesophageal fistula (EA\/TEF). The cause of EA\/TEF remains largely unknown. Therefore, to mimic the early development of the esophagus and trachea, we differentiated induced pluripotent stem cells (iPSCs) from EA\/TEF patients, and iPSCs and embryonic stem cells from healthy individuals into mature three-dimensional esophageal organoids. CXCR4, SOX17 and GATA4 expression was similar in both patient-derived and healthy endodermal cells. The expression of the key transcription factor SOX2 was significantly lower in the patient-derived anterior foregut. We also observed an abnormal expression of NKX2.1 (or NKX2-1) in the patient-derived mature esophageal organoids. At the anterior foregut stage, RNA sequencing revealed the critical genes GSTM1 and RAB37 to be significantly lower in the patient-derived anterior foregut. We therefore hypothesize that a transient dysregulation of SOX2 and the abnormal expression of NKX2.1 in patient-derived cells could be responsible for the abnormal foregut compartmentalization.<\/jats:p>","DOI":"10.1242\/dmm.049541","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T08:12:38Z","timestamp":1667290358000},"source":"Crossref","is-referenced-by-count":9,"title":["iPSCs derived from esophageal atresia patients reveal SOX2 dysregulation at the anterior foregut stage"],"prefix":"10.1242","volume":"15","author":[{"given":"Suleen","family":"Raad","sequence":"first","affiliation":[{"name":"Esophageal Development and Engineering Laboratory, CHU Sainte-Justine Research Center 1 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-486X","authenticated-orcid":false,"given":"Anu","family":"David","sequence":"additional","affiliation":[{"name":"Esophageal Development and Engineering Laboratory, CHU Sainte-Justine Research Center 1 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Sagniez","sequence":"additional","affiliation":[{"name":"CHU Sainte-Justine Research Center 2 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"},{"name":"Faculty of Medicine, University of Montreal 3 Department of Biochemistry and Molecular Medicine , , Montr\u00e9al, Quebec H3T 1J4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastien","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"CHU Sainte-Justine Research Center 2 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"},{"name":"Faculty of Medicine, University of Montreal 3 Department of Biochemistry and Molecular Medicine , , Montr\u00e9al, Quebec H3T 1J4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakaria","family":"Orfi","sequence":"additional","affiliation":[{"name":"CHU Sainte-Justine Research Center 2 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas A.","family":"Dumont","sequence":"additional","affiliation":[{"name":"CHU Sainte-Justine Research Center 2 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"},{"name":"School of Rehabilitation, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al 4 , Montr\u00e9al, Quebec H3T 1J4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"Smith","sequence":"additional","affiliation":[{"name":"CHU Sainte-Justine Research Center 2 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"},{"name":"Faculty of Medicine, University of Montreal 3 Department of Biochemistry and Molecular Medicine , , Montr\u00e9al, Quebec H3T 1J4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-8935","authenticated-orcid":false,"given":"Christophe","family":"Faure","sequence":"additional","affiliation":[{"name":"Esophageal Development and Engineering Laboratory, CHU Sainte-Justine Research Center 1 , 3175 C\u00f4te Sainte-Catherine, Montr\u00e9al, Quebec H3T 1C5 , Canada"},{"name":"Esophageal Atresia Clinic and Division of Pediatric Gastroenterology Hepatology and Nutrition, CHU Sainte-Justine 5 , 3715 C\u00f4te Sainte-Catherine , , Montr\u00e9al, Quebec H3T1C5 , Canada"},{"name":"Universit\u00e9 de Montr\u00e9al 5 , 3715 C\u00f4te Sainte-Catherine , , Montr\u00e9al, Quebec H3T1C5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"2022112809513138700_DMM049541C1","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1002\/dvdy.24219","article-title":"One shall become two: separation of the esophagus and trachea from the common foregut tube","volume":"244","author":"Billmyre","year":"2015","journal-title":"Dev. 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