{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T08:58:37Z","timestamp":1762073917010,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sophia Foundation for Medical Research project","award":["S14-12","114025011"],"award-info":[{"award-number":["S14-12","114025011"]}]},{"DOI":"10.13039\/501100001826","name":"ZonMw project","doi-asserted-by":"publisher","award":["S14-12","114025011"],"award-info":[{"award-number":["S14-12","114025011"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. As the lung develops, cells become specified and differentiate into the various cell lineages. This process is controlled by specific transcription factors, such as the SRY-related HMG-box genes SOX2 and SOX21, that are activated or repressed through intrinsic and extrinsic signals. Disturbances in any of these processes during the development of the lung may lead to various pediatric lung disorders, such as Congenital Diaphragmatic Hernia (CDH), Congenital Pulmonary Airway Malformation (CPAM) and Broncho-Pulmonary Dysplasia (BPD). Changes in the composition of the airways and the alveoli may result in reduced respiratory function and eventually lead to chronic lung disorders. In this concise review, we describe different intrinsic and extrinsic cellular processes required for proper differentiation of the epithelium during development and regeneration, and the influence of the microenvironment on this process with special focus on SOX2 and SOX21.<\/jats:p>","DOI":"10.3390\/ijms232113064","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T20:37:58Z","timestamp":1666903078000},"page":"13064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SOX2 and SOX21 in Lung Epithelial Differentiation and Repair"],"prefix":"10.3390","volume":"23","author":[{"given":"Evelien","family":"Eenjes","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus MC-Sophia Children\u2019s Hospital, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick","family":"Tibboel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus MC-Sophia Children\u2019s Hospital, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene M. H.","family":"Wijnen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus MC-Sophia Children\u2019s Hospital, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4910-8293","authenticated-orcid":false,"given":"Johannes Marco","family":"Schnater","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus MC-Sophia Children\u2019s Hospital, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-4971","authenticated-orcid":false,"given":"Robbert J.","family":"Rottier","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Erasmus MC-Sophia Children\u2019s Hospital, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Cell Biology, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1038\/s41467-018-04155-2","article-title":"Tracing the origin of heterogeneity and symmetry breaking in the early mammalian embryo","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"unstructured":"Solnica-Krezel, L. (2020). 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