ArticleDiabetes2010
The transcription factor Rfx3 regulates beta-cell differentiation, function, and glucokinase expression.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.Life science alliance · 2026Article
- Predictive control of human pancreatic cell fate using a digital model ofbioRxiv : the preprint server for biology · 2026Article
- Charting Endocrine Progenitors Across Species and Organs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Centriolar Protein POC5 Regulates Human Adipogenesis and Cellular Senescence: Insights From a Novel Metabolic Ciliopathy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Network-based insights into miRNA regulation of β-cell insulin secretion in type 2 diabetes.iScience · 2025Article
- Review
- RFX3 is essential for the generation of functional human pancreatic islets from stem cells.Diabetologia · 2025Article
- Multi-omic analysis of the ciliogenic transcription factorbioRxiv : the preprint server for biology · 2025Article
- A mechanism-informed deep neural network enables prioritization of regulators that drive cell state transitions.Nature communications · 2025Article
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas.Nature communications · 2024Article
- Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes.Developmental cell · 2023Article
- Nutrient regulation of the islet epigenome controls adaptive insulin secretion.The Journal of clinical investigation · 2023Article
- Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression.Diabetologia · 2023Article
- Article
- Ranking reprogramming factors for cell differentiation.Nature methods · 2022Article
- CellRank for directed single-cell fate mapping.Nature methods · 2022Article
- Integrating single cell transcriptomics and volume electron microscopy confirms the presence of pancreatic acinar-like cells in sea urchins.Frontiers in cell and developmental biology · 2022Article
- Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation.Communications biology · 2021Article
- The Transcriptome and Epigenome Reveal Novel Changes in Transcription Regulation During Pancreatic Rat Islet Maturation.Endocrinology · 2021Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectivePancreatic islets of perinatal mice lacking the transcription factor Rfx3 exhibit a marked reduction in insulin-producing beta-cells. The objective of this work was to unravel the cellular and molecular mechanisms underlying this deficiency. RESEARCH DESIGN AND
methodsImmunofluorescence studies and quantitative RT-PCR experiments were used to study the emergence of insulin-positive cells, the expression of transcription factors implicated in the differentiation of beta-cells from endocrine progenitors, and the expression of mature beta-cell markers during development in Rfx3(-/-) and pancreas-specific Rfx3-knockout mice. RNA interference experiments were performed to document the consequences of downregulating Rfx3 expression in Min6 beta-cells. Quantitative chromatin immunoprecipitation (ChIP), ChIP sequencing, and bandshift experiments were used to identify Rfx3 target genes.
resultsReduced development of insulin-positive cells in Rfx3(-/-) mice was not due to deficiencies in endocrine progenitors or beta-lineage specification, but reflected the accumulation of insulin-positive beta-cell precursors and defective beta-cells exhibiting reduced insulin, Glut-2, and Gck expression. Similar incompletely differentiated beta-cells developed in pancreas-specific Rfx3-deficient embryos. Defective beta-cells lacking Glut-2 and Gck expression dominate in Rfx3-deficent adults, leading to glucose intolerance. Attenuated Glut-2 and glucokinase expression, and impaired glucose-stimulated insulin secretion, were also induced by RNA interference-mediated inhibition of Rfx3 expression in Min6 cells. Finally, Rfx3 was found to bind in Min6 cells and human islets to two well-known regulatory sequences, Pal-1 and Pal-2, in the neuroendocrine promoter of the glucokinase gene.
conclusionsOur results show that Rfx3 is required for the differentiation and function of mature beta-cells and regulates the beta-cell promoter of the glucokinase gene.
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