ArticleGastroenterology2009
Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 82 citations in OpenAlex.
- Latent plasticity of the human pancreas across development, health, and disease.bioRxiv : the preprint server for biology · 2025Article
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- Low expression of CCKBR in the acinar cells is associated with insufficient starch hydrolysis in ruminants.Communications biology · 2024Article
- β-Cell Regeneration Is Driven by Pancreatic Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- GABA treatment does not induce neogenesis of new endocrine cells from pancreatic ductal cells.Islets · 2023Article
- Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration.International journal of molecular sciences · 2022Article
- Dysregulated insulin secretion is associated with pancreatic β-cell hyperplasia and direct acinar-β-cell trans-differentiation in partially eNOS-deficient mice.Physiological reports · 2022Article
- Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.Frontiers in endocrinology · 2021Review
- Protocol for Studying Reprogramming of Mouse Pancreatic Acinar Cells to β-like Cells.STAR protocols · 2020Article
- Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.International journal of molecular sciences · 2020Review
- Novel Mouse miRNA Chr13_novelMiR7354-5p Improves Bone-Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells.Molecular therapy. Nucleic acids · 2020Article
- Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture.Scientific reports · 2019Article
- Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes.Cell metabolism · 2018Review
- Acinar cells in the neonatal pancreas grow by self-duplication and not by neogenesis from duct cells.Scientific reports · 2017Article
- Systematic single-cell analysis provides new insights into heterogeneity and plasticity of the pancreas.Molecular metabolism · 2017Review
- Acinar phenotype is preserved in human exocrine pancreas cells cultured at low temperature: implications for lineage-tracing of β-cell neogenesis.Bioscience reports · 2016Article
- β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.Journal of diabetes investigation · 2016Review
- PNA lectin for purifying mouse acinar cells from the inflamed pancreas.Scientific reports · 2016Article
- Notch Signaling in Pancreatic Development.International journal of molecular sciences · 2015Review
- Reprogramming of human pancreatic exocrine cells to β-like cells.Cell death and differentiation · 2015Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsExocrine acinar cells in the pancreas are highly differentiated cells that retain a remarkable degree of plasticity. After isolation and an initial phase of dedifferentiation in vitro, rodent acinar cells can convert to endocrine beta-cells when cultured in the presence of appropriate factors. The mechanisms regulating this phenotypic conversion are largely unknown.
methodsUsing rat acinar cell cultures, we studied the role of Notch signaling in a model of acinar-to-beta-cell conversion.
resultsWe report a novel lectin-based cell labeling method to demonstrate the acinar origin of newly formed insulin-expressing beta-cells. This method allows for specific tracing of the acinar cells. We demonstrate that growth factor-induced conversion of adult acinar cells to beta-cells is negatively regulated by Notch1 signaling. Activated Notch1 signaling prevents the reexpression of the proendocrine transcription factor Neurogenin-3, the key regulator of endocrine development in the embryonic pancreas. Interfering with Notch1 signaling allows modulating the acinar cell susceptibility to the differentiation-inducing factors. Its inhibition significantly improves beta-cell neoformation with approximately 30% of acinar cells that convert to beta-cells. The newly formed beta-cells mature when transplanted ectopically and are capable of restoring normal blood glycemia in diabetic recipients.
conclusionsWe report for the first time an efficient way to reprogram one third of the acinar cells to beta-cells by adult cell type conversion. This could find application in cell replacement therapy of type 1 diabetes, provided that it can be translated from rodent to human models.
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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.