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2021-08

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cc by (c) Rovira, Meritxell et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/180146

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

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Recurs relacionat

https://doi.org/10.1101/gad.348501.121

Resum

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.

Matèries

Pàncrees, Organogènesi, Biologia molecular

Matèries (anglès)

Pancreas, Organogenesis, Molecular biology

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Articles publicats en revistes (Ciències Fisiològiques)
<b>Publicacions de projectes de recerca finançats per la UE</b>
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

ROVIRA, Meritxell, ATLA, Goutham, MAESTRO, Miguel angel, GRAU, Vanessa, GARCÍA HURTADO, Javier, FERRER, Jorge, MAQUEDA, Maria, MOSQUERA MAYO, José luís, KERR-CONTE, Julie, PATTOU, Francois. REST is a major negative regulator of endocrine differentiation during pancreas organogenesis. _Genes & Development_. 2021. Vol. 35, núm. 17-18, pàgs. 1229-1243. [consulta: 23 de gener de 2026]. ISSN: 0890-9369. [Disponible a: https://hdl.handle.net/2445/180146]

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