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dc.contributor.authorZwiggelaar, Rosalie
dc.contributor.authorLindholm, Håvard Takle
dc.contributor.authorFosslie, Madeleine Lystad
dc.contributor.authorPedersen, Marianne Terndrup
dc.contributor.authorOhta, Yuki
dc.contributor.authorDíez-Sánchez, Alberto
dc.contributor.authorMartín-Alonso, Mara
dc.contributor.authorOstrop, Jenny
dc.contributor.authorMatono, Mami
dc.contributor.authorParmar, Naveen
dc.contributor.authorKvaløy, Emilie
dc.contributor.authorSpanjers, Roos
dc.contributor.authorNazmi, Kamran
dc.contributor.authorRye, Morten Beck
dc.contributor.authorDrabløs, Finn
dc.contributor.authorArrowsmith, Cheryl H
dc.contributor.authorDahl, John Arne
dc.contributor.authorJensen, Kim B.
dc.contributor.authorSato, Toshiro
dc.contributor.authorOudhoff, Menno
dc.date.accessioned2020-09-29T06:49:56Z
dc.date.available2020-09-29T06:49:56Z
dc.date.created2020-09-25T11:50:54Z
dc.date.issued2020
dc.identifier.issn2375-2548
dc.identifier.urihttps://hdl.handle.net/11250/2680089
dc.description.abstractIntestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth cells, appear after birth in the neonatal period. We aimed to identify regulators of neonatal intestinal epithelial development by testing a small library of epigenetic modifier inhibitors in Paneth cell–skewed organoid cultures. We found that lysine-specific demethylase 1A (Kdm1a/Lsd1) is absolutely required for Paneth cell differentiation. Lsd1-deficient crypts, devoid of Paneth cells, are still able to form organoids without a requirement of exogenous or endogenous Wnt. Mechanistically, we find that LSD1 enzymatically represses genes that are normally expressed only in fetal and neonatal epithelium. This gene profile is similar to what is seen in repairing epithelium, and we find that Lsd1-deficient epithelium has superior regenerative capacities after irradiation injury. In summary, we found an important regulator of neonatal intestinal development and identified a druggable target to reprogram intestinal epithelium toward a reparative state.en_US
dc.language.isoengen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.relation.urihttps://advances.sciencemag.org/content/6/37/eabc0367
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/deed.no*
dc.titleLSD1 represses a neonatal/reparative gene program in adult intestinal epitheliumen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.source.volume6en_US
dc.source.journalScience Advancesen_US
dc.source.issue37en_US
dc.identifier.doi10.1126/sciadv.abc0367
dc.identifier.cristin1833399
dc.relation.projectNorges forskningsråd: 274760en_US
dc.relation.projectKreftforeningen: 182767en_US
dc.relation.projectNorges forskningsråd: 223255en_US
dc.description.localcodeCopyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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