ArticleDiabetes2011
Production of functional glucagon-secreting α-cells from human embryonic stem cells.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 229 citations in OpenAlex.
- Markers of beta cell and alpha cell mass in human stem cell-generated implants with glycemic control at human setpoint.Stem cells translational medicine · 2026Article
- Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets.Nature communications · 2026Article
- Advances in Internal Organogenesis: Differentiation and Morphogenesis of Human Ventral Cavity Organs.Stem cell reviews and reports · 2026Review
- Differentiation of patient-specific induced pluripotent stem cells derived from type 1 diabetes peripheral blood mononuclear cells into pancreatic β-like cells.World journal of stem cells · 2025Article
- Tracking Insulin- and Glucagon-Expressing Cells In Vitro and In Vivo Using a Double-Reporter Human Embryonic Stem Cell Line.Diabetes · 2025Article
- LINC MIR503HG Controls SC-β Cell Differentiation and Insulin Production by Targeting CDH1 and HES1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Prediction of diabetes mellitus after kidney transplantation using patient-specific induced pluripotent stem cells.Kidney research and clinical practice · 2024Article
- Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells.Stem cell research & therapy · 2024Article
- The human α cell in health and disease.The Journal of endocrinology · 2023Review
- Pancreatic β-cell heterogeneity in adult human islets and stem cell-derived islets.Cellular and molecular life sciences : CMLS · 2023Review
- Protocol development to further differentiate and transition stem cell-derived pancreatic progenitors from a monolayer into endocrine cells in suspension culture.Scientific reports · 2023Article
- Effective Generation of Functional Pancreatic β Cells from Human-Derived Dental Stem Cells of Apical Papilla and Bone-Marrow-Derived Stem Cells: A Comparative Study.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Single-cell analyses reveal distinct expression patterns and roles of long non-coding RNAs during hESC differentiation into pancreatic progenitors.Stem cell research & therapy · 2023Article
- CDK8/19 inhibition plays an important role in pancreatic β-cell induction from human iPSCs.Stem cell research & therapy · 2023Article
- Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.Nature biotechnology · 2022Article
- Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling.Nature communications · 2022Article
- The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?Frontiers in endocrinology · 2022Review
- Adapting Physiology in Functional Human Islet Organogenesis.Frontiers in cell and developmental biology · 2022Article
- Engineering islets from stem cells for advanced therapies of diabetes.Nature reviews. Drug discovery · 2021Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDifferentiation of human embryonic stem (hES) cells to fully developed cell types holds great therapeutic promise. Despite significant progress, the conversion of hES cells to stable, fully differentiated endocrine cells that exhibit physiologically regulated hormone secretion has not yet been achieved. Here we describe an efficient differentiation protocol for the in vitro conversion of hES cells to functional glucagon-producing α- cells. RESEARCH DESIGN AND
methodsUsing a combination of small molecule screening and empirical testing, we developed a six-stage differentiation protocol for creating functional α-cells. An extensive in vitro and in vivo characterization of the differentiated cells was performed.
resultsA high rate of synaptophysin expression (>75%) and robust expression of glucagon and the α-cell transcription factor ARX was achieved. After a transient polyhormonal state in which cells coexpress glucagon and insulin, maturation in vitro or in vivo resulted in depletion of insulin and other β-cell markers with concomitant enrichment of α-cell markers. After transplantation, these cells secreted fully processed, biologically active glucagon in response to physiologic stimuli including prolonged fasting and amino acid challenge. Moreover, glucagon release from transplanted cells was sufficient to reduce demand for pancreatic glucagon, resulting in a significant decrease in pancreatic α-cell mass.
conclusionsThese results indicate that fully differentiated pancreatic endocrine cells can be created via stepwise differentiation of hES cells. These cells may serve as a useful screening tool for the identification of compounds that modulate glucagon secretion as well as those that promote the transdifferentiation of α-cells to β-cells.
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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.