ArticleCell metabolism2024
Repression of latent NF-κB enhancers by PDX1 regulates β cell functional heterogeneity.
Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
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- Regulation of m6A methylation in the immune microenvironment in the development of diabetes mellitus.Journal of translational medicine · 2025Review
- Circadian regulation of insulin secretion in transplanted human stem cell-derived pancreatic β-cells.Stem cell reports · 2025Article
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Established dietary interventions and time-restricted eating for cardiovascular disease prevention.Cell reports. Medicine · 2025Review
- Targeting Ras homolog enriched in brain 1 to restore β-cell mass and function: A potential therapeutic strategy for diabetes.World journal of diabetes · 2025Article
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- Endocrine-exocrine miR-503-322 drives aging-associated pancreatitis via targeting MKNK1 in acinar cells.Nature communications · 2025Article
- Advance in molecular mechanisms underlying diabetes related to viral hepatitis infection.Frontiers in cellular and infection microbiology · 2025Review
- Ophiopogonin D improves pancreatic islet cell dedifferentiation to treat diabetes by regulating the GRP78/ROS/PDX1 signaling pathway.Frontiers in pharmacology · 2025Article
- Apoptosis antagonizing transcription factor expression and its validation as a potential diagnostic and prognostic biomarker in oral squamous cell carcinoma.Frontiers in oncology · 2025Article
- Loss of O-GlcNAcylation modulates mTORC1 and autophagy in β cells, driving diabetes 2 progression.JCI insight · 2024Article
- Core circadian transcription factor Bmal1 mediates β cell response and recovery from pro-inflammatory injury.iScience · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity and function within multicellular tissues through incompletely known mechanisms. By assembling a single-cell atlas of chromatin state within human islets, we identified β cell subtypes governed by either high or low activity of the lineage-determining factor pancreatic duodenal homeobox-1 (PDX1). β cells with reduced PDX1 activity displayed increased chromatin accessibility at latent nuclear factor κB (NF-κB) enhancers. Pdx1 hypomorphic mice exhibited de-repression of NF-κB and impaired glucose tolerance at night. Three-dimensional analyses in tandem with chromatin immunoprecipitation (ChIP) sequencing revealed that PDX1 silences NF-κB at circadian and inflammatory enhancers through long-range chromatin contacts involving SIN3A. Conversely, Bmal1 ablation in β cells disrupted genome-wide PDX1 and NF-κB DNA binding. Finally, antagonizing the interleukin (IL)-1β receptor, an NF-κB target, improved insulin secretion in Pdx1 hypomorphic islets. Our studies reveal functional subtypes of single β cells defined by a gradient in PDX1 activity and identify NF-κB as a target for insulinotropic therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.