Rovira, MeritxellAtla, GouthamMaestro, Miguel AngelGrau, VanessaGarcía Hurtado, JavierFerrer, JorgeMaqueda, MariaMosquera Mayo, José LuísKerr-Conte, JuliePattou, Francois2021-09-212021-09-212021-080890-9369https://hdl.handle.net/2445/180146Understanding genomic regulatory mechanisms of pancreas differentiation is relevant to the pathophysiology of diabetes mellitus, and to the development of replacement therapies. Numerous transcription factors promote β cell differentiation, although less is known about negative regulators. Earlier epigenomic studies suggested that the transcriptional repressor REST could be a suppressor of endocrine gene programs in the embryonic pancreas. However, pancreatic Rest knock-out mice failed to show increased 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 now observe a marked increase in the formation of pancreatic endocrine cells. REST inhibition also promoted endocrinogenesis in zebrafish and mouse early postnatal ducts, and induced β-cell specific genes in human adult ductderived organoids. Finally, we define REST genomic programs that suppress pancreatic endocrine differentiation. These results establish a crucial role of REST as a negative regulator of pancreatic endocrine differentiation.15 p.application/pdfengcc by (c) Rovira, Meritxell et al., 2021http://creativecommons.org/licenses/by/3.0/es/PàncreesOrganogènesiBiologia molecularPancreasOrganogenesisMolecular biologyinfo:eu-repo/semantics/article7135352021-09-21info:eu-repo/semantics/openAccess34385258