{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:16:35Z","timestamp":1768511795978,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,15]]},"group-title":"Genetics","reference-count":44,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Replenishment of pancreatic beta cells is a key to the cure for diabetes. Beta cells regeneration is achieved predominantly by self-replication especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into beta cells. How pancreatic duct cells undergo transdifferentiated and whether we could manipulate the transdifferentiation to replenish beta cell mass is not well understood. Using a genome-wide CRISPR screen, we discovered that loss-of-function of ALDH3B2 is sufficient to transdifferentiate human pancreatic duct cells into functional beta-like cells. The transdifferentiated cells have significant increase in beta cell marker genes expression, secrete insulin in response to glucose, and reduce blood glucose when transplanted into diabetic mice. Our study identifies a novel gene that could potentially be targeted in human pancreatic duct cells to replenish beta cell mass for diabetes therapy.<\/jats:p>","DOI":"10.1101\/2024.05.13.593941","type":"posted-content","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T20:55:20Z","timestamp":1715806520000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss-of-function of ALDH3B2 transdifferentiates human pancreatic duct cells into beta-like cells"],"prefix":"10.64898","author":[{"given":"Jian","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Bode","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-chi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelle","family":"Morrow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siying","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"da Silva Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Lee-Papastavros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Hollister-Lock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Bonner-Weir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024052009150558000_2024.05.13.593941v1.1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.39.4.401"},{"key":"2024052009150558000_2024.05.13.593941v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2015.03.004"},{"key":"2024052009150558000_2024.05.13.593941v1.3","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.stemcr.2015.02.017","article-title":"Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines","volume":"4","year":"2015","journal-title":"Stem Cell Reports"},{"key":"2024052009150558000_2024.05.13.593941v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.040"},{"key":"2024052009150558000_2024.05.13.593941v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200007273430401"},{"key":"2024052009150558000_2024.05.13.593941v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.08.007"},{"key":"2024052009150558000_2024.05.13.593941v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature02520"},{"key":"2024052009150558000_2024.05.13.593941v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1809-6"},{"key":"2024052009150558000_2024.05.13.593941v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.002"},{"key":"2024052009150558000_2024.05.13.593941v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.035"},{"key":"2024052009150558000_2024.05.13.593941v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature07314"},{"key":"2024052009150558000_2024.05.13.593941v1.12","doi-asserted-by":"publisher","DOI":"10.3109\/03009734.2016.1154906"},{"key":"2024052009150558000_2024.05.13.593941v1.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-543X.2004.00075.x"},{"key":"2024052009150558000_2024.05.13.593941v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805803105"},{"key":"2024052009150558000_2024.05.13.593941v1.15","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1016\/j.celrep.2018.02.006","article-title":"P2RY1\/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics","volume":"22","year":"2018","journal-title":"Cell Rep"},{"key":"2024052009150558000_2024.05.13.593941v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1918314117"},{"key":"2024052009150558000_2024.05.13.593941v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.048"},{"key":"2024052009150558000_2024.05.13.593941v1.18","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1038\/s41467-024-47972-4","article-title":"Acinar to beta-like cell conversion through inhibition of focal adhesion kinase","volume":"15","year":"2024","journal-title":"Nat Commun"},{"key":"2024052009150558000_2024.05.13.593941v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.14.7999"},{"key":"2024052009150558000_2024.05.13.593941v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910150505"},{"key":"2024052009150558000_2024.05.13.593941v1.21","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/00006676-198810000-00003","article-title":"Morphological and biochemical characterization of a human pancreatic ductal cell line (PANC-1)","volume":"3","year":"1988","journal-title":"Pancreas"},{"key":"2024052009150558000_2024.05.13.593941v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2009.114"},{"key":"2024052009150558000_2024.05.13.593941v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3047"},{"key":"2024052009150558000_2024.05.13.593941v1.24","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.6.697"},{"key":"2024052009150558000_2024.05.13.593941v1.25","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3904645"},{"key":"2024052009150558000_2024.05.13.593941v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12631"},{"key":"2024052009150558000_2024.05.13.593941v1.27","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1670"},{"key":"2024052009150558000_2024.05.13.593941v1.28","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-03-0203"},{"key":"2024052009150558000_2024.05.13.593941v1.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713736114"},{"key":"2024052009150558000_2024.05.13.593941v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40893-8"},{"key":"2024052009150558000_2024.05.13.593941v1.31","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1013"},{"key":"2024052009150558000_2024.05.13.593941v1.32","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1007\/s00125-017-4362-8","article-title":"Transplantation sites for human and murine islets","volume":"60","year":"2017","journal-title":"Diabetologia"},{"key":"2024052009150558000_2024.05.13.593941v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.124"},{"key":"2024052009150558000_2024.05.13.593941v1.34","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1182\/blood.V85.10.2742.bloodjournal85102742","article-title":"Assessment of aldehyde dehydrogenase in viable cells","volume":"85","year":"1995","journal-title":"Blood"},{"key":"2024052009150558000_2024.05.13.593941v1.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9118"},{"key":"2024052009150558000_2024.05.13.593941v1.36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02184.x"},{"key":"2024052009150558000_2024.05.13.593941v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2010.05.001"},{"key":"2024052009150558000_2024.05.13.593941v1.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912589107"},{"key":"2024052009150558000_2024.05.13.593941v1.39","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20140624"},{"key":"2024052009150558000_2024.05.13.593941v1.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113081108"},{"key":"2024052009150558000_2024.05.13.593941v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.016"},{"key":"2024052009150558000_2024.05.13.593941v1.42","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247005"},{"key":"2024052009150558000_2024.05.13.593941v1.43","doi-asserted-by":"publisher","DOI":"10.1089\/cell.2014.0025"},{"key":"2024052009150558000_2024.05.13.593941v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(02)00061-0"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.05.13.593941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:26:50Z","timestamp":1768458410000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.05.13.593941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":44,"URL":"https:\/\/doi.org\/10.1101\/2024.05.13.593941","relation":{},"subject":[],"published":{"date-parts":[[2024,5,15]]},"subtype":"preprint"}}