ArticleMolecular metabolism2015
A human beta cell line with drug inducible excision of immortalizing transgenes.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Article
- Islet ultrastructure: past achievements and future directions.Diabetologia · 2026Review
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- Redefining β-Cell Function in Type 2 Diabetes Mellitus: From Comprehensive Assessment to Precision Medicine.Diabetes & metabolism journal · 2026Review
- In vivo functional profiling and structural characterization of the humanScience advances · 2026Article
- Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.Diabetologia · 2026Article
- Massively parallel reporter assay reveals promoter-, position-, and strand-specific effects in transcription start sites.bioRxiv : the preprint server for biology · 2025Article
- HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes.Cell metabolism · 2025Article
- Article
- Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science (New York, N.Y.) · 2025Article
- Article
- Role of Sec61α2 Translocon in Insulin Biosynthesis.Diabetes · 2024Article
- Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin gene transcription and content in β cells.Clinical science (London, England : 1979) · 2024Article
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
- Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.Molecular metabolism · 2024Review
- Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8Nature communications · 2024Article
- Senescence of human pancreatic beta cells enhances functional maturation through chromatin reorganization and promotes interferon responsiveness.Nucleic acids research · 2024Article
- Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic β-cell survival and function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Light-Mediated Enhancement of Glucose-Stimulated Insulin Release of Optogenetically Engineered Human Pancreatic Beta-Cells.ACS synthetic biology · 2024Article
- Redox regulation of mNature cell biology · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesAccess to immortalized human pancreatic beta cell lines that are phenotypically close to genuine adult beta cells, represent a major tool to better understand human beta cell physiology and develop new therapeutics for Diabetes. Here we derived a new conditionally immortalized human beta cell line, EndoC-βH3 in which immortalizing transgene can be efficiently removed by simple addition of tamoxifen.
methodsWe used lentiviral mediated gene transfer to stably integrate a tamoxifen inducible form of CRE (CRE-ERT2) into the recently developed conditionally immortalized EndoC βH2 line. The resulting EndoC-βH3 line was characterized before and after tamoxifen treatment for cell proliferation, insulin content and insulin secretion.
resultsWe showed that EndoC-βH3 expressing CRE-ERT2 can be massively amplified in culture. We established an optimized tamoxifen treatment to efficiently excise the immortalizing transgenes resulting in proliferation arrest. In addition, insulin expression raised by 12 fold and insulin content increased by 23 fold reaching 2 μg of insulin per million cells. Such massive increase was accompanied by enhanced insulin secretion upon glucose stimulation. We further observed that tamoxifen treated cells maintained a stable function for 5 weeks in culture.
conclusionsEndoC βH3 cell line represents a powerful tool that allows, using a simple and efficient procedure, the massive production of functional non-proliferative human beta cells. Such cells are close to genuine human beta cells and maintain a stable phenotype for 5 weeks in culture.
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