Rovira Clusellas, MeritxellAtla, GouthamMaestro, Miguel ÁngelGrau, VanessaGarcía-Hurtado, JavierMaqueda, MariaMosquera, Jose LuisYamada, YasuhiroKerr-Conte, JuliePattou, FrancoisFerrer, Jorge2022-01-192022-01-192021Rovira M, Atla G, Maestro MA, Grau V, García-Hurtado, J Maqueda M et al. REST is a major negative regulator of endocrine differentiation during pancreas organogenesis. Genes Dev. 2021 Sep 1;35(17-18):1229-1242. DOI: 10.1101/gad.348501.1210890-9369http://hdl.handle.net/10230/52263Multiple transcription factors have been shown to promote pancreatic β-cell differentiation, yet much less is known about negative regulators. Earlier epigenomic studies suggested that the transcriptional repressor REST could be a suppressor of endocrinogenesis in the embryonic pancreas. However, pancreatic Rest knockout mice failed to show abnormal numbers of endocrine cells, suggesting that REST is not a major regulator of endocrine differentiation. Using a different conditional allele that enables profound REST inactivation, we observed a marked increase in pancreatic endocrine cell formation. REST inhibition also promoted endocrinogenesis in zebrafish and mouse early postnatal ducts and induced β-cell-specific genes in human adult duct-derived organoids. We also defined genomic sites that are bound and repressed by REST in the embryonic pancreas. Our findings show that REST-dependent inhibition ensures a balanced production of endocrine cells from embryonic pancreatic progenitors.application/pdfeng© 2021 Meritxell Rovira et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International),as described at http://creativecommons.org/licenses/by/4.0/EndocrinologiaPàncreesGenèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1101/gad.348501.121info:eu-repo/semantics/openAccess