{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:48:21Z","timestamp":1792453701106,"version":"4.5.0"},"reference-count":42,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,10,28]]},"abstract":"<jats:p>Regulatory proteins have been identified in embryonic development of the endocrine pancreas. It is unknown whether these factors can also play a role in the formation of pancreatic endocrine cells from postnatal nonendocrine cells. The present study demonstrates that adult human pancreatic duct cells can be converted into insulin-expressing cells after ectopic, adenovirus-mediated expression of the class B basic helix-loop-helix factor neurogenin 3 (ngn3), which is a critical factor in embryogenesis of the mouse endocrine pancreas. Infection with adenovirus ngn3 (Adngn3) induced gene and\/or protein expression of NeuroD\/\u03b22, Pax4, Nkx2.2, Pax6, and Nkx6.1, all known to be essential for \u03b2-cell differentiation in mouse embryos. Expression of ngn3 in adult human duct cells induced Notch ligands Dll1 and Dll4 and neuroendocrine- and \u03b2-cell\u2013specific markers: it increased the percentage of synaptophysin- and insulin-positive cells 15-fold in ngn3-infected versus control cells. Infection with NeuroD\/\u03b22 (a downstream target of ngn3) induced similar effects. These data indicate that the Delta-Notch pathway, which controls embryonic development of the mouse endocrine pancreas, can also operate in adult human duct cells driving them to a neuroendocrine phenotype with the formation of insulin-expressing cells.<\/jats:p>","DOI":"10.1083\/jcb.200203074","type":"journal-article","created":{"date-parts":[[2002,10,28]],"date-time":"2002-10-28T20:02:20Z","timestamp":1035835340000},"page":"303-312","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":228,"title":["Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3"],"prefix":"10.1083","volume":"159","author":[{"given":"Yves","family":"Heremans","sequence":"first","affiliation":[{"name":"1Diabetes Research Center, Brussels Free University (VUB), B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Van De Casteele","sequence":"additional","affiliation":[{"name":"1Diabetes Research Center, Brussels Free University (VUB), B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"in't Veld","sequence":"additional","affiliation":[{"name":"1Diabetes Research Center, Brussels Free University (VUB), B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Gradwohl","sequence":"additional","affiliation":[{"name":"2Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, U381, Development and Pathology of the Digestive System, F-67200 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palle","family":"Serup","sequence":"additional","affiliation":[{"name":"3Hagedorn Research Institute, DK-2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Madsen","sequence":"additional","affiliation":[{"name":"3Hagedorn Research Institute, DK-2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pipeleers","sequence":"additional","affiliation":[{"name":"1Diabetes Research Center, Brussels Free University (VUB), B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Heimberg","sequence":"additional","affiliation":[{"name":"1Diabetes Research Center, Brussels Free University (VUB), B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2002,10,28]]},"reference":[{"key":"2023072213515739700_BIB1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/23716","volume":"400","year":"1999","journal-title":"Nature."},{"key":"2023072213515739700_BIB2","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1126\/science.284.5415.770","volume":"284","year":"1999","journal-title":"Science."},{"key":"2023072213515739700_BIB3","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.2337\/diabetes.50.8.1691","volume":"50","year":"2001","journal-title":"Diabetes."},{"key":"2023072213515739700_BIB4","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1074\/jbc.272.3.1929","volume":"272","year":"1997","journal-title":"J. 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