| First Author | Rovira M | Year | 2021 |
| Journal | Genes Dev | Volume | 35 |
| Issue | 17-18 | Pages | 1229-1242 |
| PubMed ID | 34385258 | Mgi Jnum | J:321932 |
| Mgi Id | MGI:7254944 | Doi | 10.1101/gad.348501.121 |
| Citation | Rovira M, et al. (2021) REST is a major negative regulator of endocrine differentiation during pancreas organogenesis. Genes Dev 35(17-18):1229-1242 |
| abstractText | 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. |
