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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/180146
REST is a major negative regulator of endocrine differentiation during pancreas organogenesis
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Understanding 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.
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ROVIRA, Meritxell, et al. REST is a major negative regulator of endocrine differentiation during pancreas organogenesis. Genes & Development. 2021. Vol. 35, num. 17-18, pags. 1229-1243. ISSN 0890-9369. [consulted: 17 of June of 2026]. Available at: https://hdl.handle.net/2445/180146