Rest Is A Major Negative Regulator Of Endocrine Differentiation During Pancreas Organogenesis
GENES & DEVELOPMENT(2021)
摘要
Multiple transcription factors have been shown to promote pancreatic beta-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 beta-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.
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关键词
REST, beta cells, bipotent progenitors, endocrine differentiation, pancreas, pancreas development, transcriptional repressors
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