PUBLICATION
REST is a major negative regulator of endocrine differentiation during pancreas organogenesis
- Authors
- Rovira, M., Atla, G., Maestro, M.A., Grau, V., García-Hurtado, J., Maqueda, M., Mosquera, J.L., Yamada, Y., Kerr-Conte, J., Pattou, F., Ferrer, J.
- ID
- ZDB-PUB-210814-6
- Date
- 2021
- Source
- Genes & Development 35(17-18): 1229-1242 (Journal)
- Registered Authors
- Keywords
- REST, bipotent progenitors, endocrine differentiation, pancreas, pancreas development, transcriptional repressors, β cells
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Gene Expression Regulation, Developmental*
- Mice
- Organogenesis/genetics
- Pancreas
- Zebrafish*/genetics
- PubMed
- 34385258 Full text @ Genes & Dev.
Citation
Rovira, M., Atla, G., Maestro, M.A., Grau, V., García-Hurtado, J., Maqueda, M., Mosquera, J.L., Yamada, Y., Kerr-Conte, J., Pattou, F., Ferrer, J. (2021) REST is a major negative regulator of endocrine differentiation during pancreas organogenesis. Genes & Development. 35(17-18):1229-1242.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping