ArticleThe Journal of clinical investigation2017
LIM domain-binding 1 maintains the terminally differentiated state of pancreatic β cells.
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 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Workload-induced changes to cell state contribute to β-cell failure in diabetes.bioRxiv : the preprint server for biology · 2026Article
- LDB1 regulates gene expression and chromatin structure in pluripotency and lineage differentiation.Nucleic acids research · 2026Article
- Retinol-binding protein 4 in cardiovascular diseases: mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2026Review
- The Islet-1 Interaction Partner Rnf20 Regulates Glucose Homeostasis and Pancreatic β-Cell Identity.Diabetes · 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
- Transcriptional coactivator MED15 is required for beta cell maturation.Nature communications · 2024Article
- Development, regeneration, and physiological expansion of functional β-cells: Cellular sources and regulators.Frontiers in cell and developmental biology · 2024Review
- Chromatin accessibility differences between alpha, beta, and delta cells identifies common and cell type-specific enhancers.BMC genomics · 2023Article
- Nutrient regulation of the islet epigenome controls adaptive insulin secretion.The Journal of clinical investigation · 2023Article
- Article
- Sex Differences in the Molecular Programs of Pancreatic Cells Contribute to the Differential Risks of Type 2 Diabetes.Endocrinology · 2022Article
- The Ldb1 transcriptional co-regulator is required for establishment and maintenance of the pancreatic endocrine lineage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas.Development (Cambridge, England) · 2022Article
- Review
- The Anna Karenina Model of β-Cell Maturation in Development and Their Dedifferentiation in Type 1 and Type 2 Diabetes.Diabetes · 2021Article
- CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.Cell death & disease · 2021Article
- Cooperation of LIM domain-binding 2 (LDB2) with EGR in the pathogenesis of schizophrenia.EMBO molecular medicine · 2021Article
- Functional maturation of immature β cells: A roadblock for stem cell therapy for type 1 diabetes.World journal of stem cells · 2021Review
- The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity.Endocrinology · 2021Review
- Transcription factor GLIS3: Critical roles in thyroid hormone biosynthesis, hypothyroidism, pancreatic beta cells and diabetes.Pharmacology & therapeutics · 2020Review
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
The recognition of β cell dedifferentiation in type 2 diabetes raises the translational relevance of mechanisms that direct and maintain β cell identity. LIM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes promoter-enhancer looping, thereby directing fate assignment and maturation of progenitor populations. Many terminally differentiated endocrine cell types, however, remain enriched for LDB1, but its role is unknown. Here, we have demonstrated a requirement for LDB1 in maintaining the terminally differentiated status of pancreatic β cells. Inducible ablation of LDB1 in mature β cells impaired insulin secretion and glucose homeostasis. Transcriptomic analysis of LDB1-depleted β cells revealed the collapse of the terminally differentiated gene program, indicated by a loss of β cell identity genes and induction of the endocrine progenitor factor neurogenin 3 (NEUROG3). Lineage tracing confirmed that LDB1-depleted, insulin-negative β cells express NEUROG3 but do not adopt alternate endocrine cell fates. In primary mouse islets, LDB1 and its LIM homeodomain-binding partner islet 1 (ISL1) were coenriched at chromatin sites occupied by pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), forkhead box A2 (FOXA2), and NK2 homeobox 2 (NKX2.2) - factors that co-occupy active enhancers in 3D chromatin domains in human islets. Indeed, LDB1 was enriched at active enhancers in human islets. Thus, LDB1 maintains the terminally differentiated state of β cells and is a component of active enhancers in both murine and human islets.
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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.