{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:47:44Z","timestamp":1790905664492,"version":"4.1.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"865","funder":[{"name":"the Beatson Foundation"},{"name":"Breakthrough T1D"},{"name":"Mary K. Iacocca Foundation"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:p>\n                    Replenishment of pancreatic \u03b2 cells is key to a cure for diabetes. \u03b2 cell regeneration is achieved predominantly by self-replication, especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into \u03b2 cells. How pancreatic duct cells are transdifferentiated and whether we can manipulate transdifferentiation to replenish \u03b2 cell mass are not well understood. Using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen, we found that the loss of function of aldehyde dehydrogenase family 3 member B2 (\n                    <jats:italic toggle=\"yes\">ALDH3B2<\/jats:italic>\n                    ) was sufficient to transdifferentiate cell line\u2013based and human pancreatic duct cells into functional \u03b2-like cells. The transdifferentiated cells had substantially increased the expression of \u03b2 cell marker genes, secreted insulin in response to glucose, and lowered blood glucose to near normal for 6 weeks after transplantation into streptozotocin-induced diabetic mice under the kidney capsule. Our study identifies a gene that could potentially be targeted in human pancreatic duct cells to replenish \u03b2 cell mass for diabetes therapy.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.ady2234","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:58:11Z","timestamp":1788371891000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Loss of function of\n                    <i>ALDH3B2<\/i>\n                    transdifferentiates human pancreatic duct cells into \u03b2-like cells"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-1383","authenticated-orcid":true,"given":"Jian","family":"Li","sequence":"first","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-2726","authenticated-orcid":true,"given":"Kevin","family":"Bode","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."},{"name":"Section for Immunology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-chi","family":"Lee","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-4273","authenticated-orcid":true,"given":"Noelle","family":"Morrow","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Ma","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9055-8109","authenticated-orcid":true,"given":"Mulin","family":"He","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1500-1504","authenticated-orcid":true,"given":"Siying","family":"Wei","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"da Silva Pereira","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Stewart","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lee-Papastavros","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4469-4932","authenticated-orcid":true,"given":"Jennifer","family":"Hollister-Lock","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke A.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-7217","authenticated-orcid":true,"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Bioinformatics &amp; 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