# name
REST is a major negative regulator of endocrine differentiation during pancreas organogenesis

# metadata.dc.description.abstract[].value
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.

# metadata.dc.rights[].value
cc by (c) Rovira, Meritxell et al., 2021

# metadata.dc.source[].value
Articles publicats en revistes (Ciències Fisiològiques)

# metadata.dc.title[].value
REST is a major negative regulator of endocrine differentiation during pancreas organogenesis