Author:
Rovira Meritxell,Atla Goutham,Maestro Miguel Angel,Grau Vane,García-Hurtado Javier,Maqueda Maria,Mosquera Jose Luis,Yamada Yasuhiro,Kerr-Conte Julie,Pattou Francois,Ferrer Jorge
Abstract
Multiple 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.
Funder
Ministerio de Ciencia, Innovación y Universidades
Medical Research Council
Wellcome Trust
European Research Council
Instituto de Salud Carlos III
Spanish Ministry of Science, Innovation, and Universities
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
18 articles.
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