ArticleThe Journal of clinical investigation2017
Pancreatic β cell identity requires continual repression of non-β cell programs.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
88 citing papers in PubMed, 135 citations in OpenAlex.
- CHD4 and NKX2.2 Cooperate to Regulate β-Cell Function by Repressing Non-β-Cell Gene Programs.Diabetes · 2026Article
- eNAMPT induces alpha-cell mass expansion but impaired glucagon counter regulatory response.Endocrinology · 2026Article
- Translating the blueprint of cell fate: eIF5A-mediated translation regulates cellular identity in the pancreas.Molecular metabolism · 2026Article
- Review
- Article
- YAP and TEAD Are Transcriptional Regulators of Neuroendocrine Differentiation and Growth in Carcinoid Cells.The American journal of pathology · 2026Article
- CHD4 and NKX2.2 Cooperate to Regulate Beta Cell Function by Repressing Non-Beta Cell Gene Programs.bioRxiv : the preprint server for biology · 2025Article
- Human NKX2.2 influences islet endocrine cell fate choices through regulation of WNT pathway genes.bioRxiv : the preprint server for biology · 2025Article
- Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science (New York, N.Y.) · 2025Article
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- Targeting Epigenetic Plasticity to Reduce Periodontitis-Related Inflammation in Diabetes: CBD, Metformin, and Other Natural Products as Potential Synergistic Candidates for Regulation? A Narrative Review.International journal of molecular sciences · 2025Review
- E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.Genes & development · 2025Article
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications.International journal of molecular sciences · 2025Review
- Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes.Life (Basel, Switzerland) · 2025Article
- Enhancing insulin secretion by pancreatic β-cell redifferentiation: a study of the anti-diabetic effects of berberineFrontiers in endocrinology · 2025Article
- β-cell heterogeneity and molecular plasticity in type 2 diabetes: multi-omics perspectives and the role of gut microbiota.Frontiers in cell and developmental biology · 2025Review
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Hormone-switching islet cells: parallels to transmitter-switching neurons.Frontiers in cell and developmental biology · 2025Article
- Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review.Journal of diabetes and metabolic disorders · 2024Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Loss of β cell identity, the presence of polyhormonal cells, and reprogramming are emerging as important features of β cell dysfunction in patients with type 1 and type 2 diabetes. In this study, we have demonstrated that the transcription factor NKX2.2 is essential for the active maintenance of adult β cell identity as well as function. Deletion of Nkx2.2 in β cells caused rapid onset of a diabetic phenotype in mice that was attributed to loss of insulin and downregulation of many β cell functional genes. Concomitantly, NKX2.2-deficient murine β cells acquired non-β cell endocrine features, resulting in populations of completely reprogrammed cells and bihormonal cells that displayed hybrid endocrine cell morphological characteristics. Molecular analysis in mouse and human islets revealed that NKX2.2 is a conserved master regulatory protein that controls the acquisition and maintenance of a functional, monohormonal β cell identity by directly activating critical β cell genes and actively repressing genes that specify the alternative islet endocrine cell lineages. This study demonstrates the highly volatile nature of the β cell, indicating that acquiring and sustaining β cell identity and function requires not only active maintaining of the expression of genes involved in β cell function, but also continual repression of closely related endocrine gene programs.
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Registered trials
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.