ArticleCell stem cell2016
An Isogenic Human ESC Platform for Functional Evaluation of Genome-wide-Association-Study-Identified Diabetes Genes and Drug Discovery.
Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications.Frontiers in endocrinology · 2022Pooled it
- Associations ofJournal of diabetes research · 2020Pooled it
- CRISPR Technologies in Type 2 Diabetes: From Mechanistic Insights to Therapeutic Discovery.International journal of molecular sciences · 2026Review
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Age-independent and targetable transcription factor networks regulating CD8Cell reports · 2026Article
- Harnessing organoid technology to model autoimmune pathways in rheumatological and inflammatory disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Comprehensive Network pharmacology and in vitro investigation of L-mimosine: unveiling multi-targeted therapeutic potential against breast cancer.BMC complementary medicine and therapies · 2025Article
- Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals.Cell reports · 2025Article
- A Compound Screen Based on Isogenic hESC-Derived β Cell Reveals an Inhibitor Targeting ZnT8-Mediated Zinc Transportation to Protect Pancreatic β Cell from Stress-Induced Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Eperisone Analogs, Rescuers ofACS medicinal chemistry letters · 2025Article
- From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes.Molecular and cellular biochemistry · 2025Review
- Organoids: their emerging essential role in pathological mechanisms and drug discovery of diabetes and its complications.Frontiers in pharmacology · 2025Review
- Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection.Cell stem cell · 2024Article
- Combined small-molecule treatment accelerates maturation of human pluripotent stem cell-derived neurons.Nature biotechnology · 2024Article
- Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.bioRxiv : the preprint server for biology · 2024Article
- Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic β-cells.iScience · 2024Article
- Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus.Stem cell research & therapy · 2024Review
- Organoid-guided precision hepatology for metabolic liver disease.Journal of hepatology · 2024Review
- Heterozygous missense variant in GLI2 impairs human endocrine pancreas development.Nature communications · 2024Article
- Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Genome-wide association studies (GWASs) have increased our knowledge of loci associated with a range of human diseases. However, applying such findings to elucidate pathophysiology and promote drug discovery remains challenging. Here, we created isogenic human ESCs (hESCs) with mutations in GWAS-identified susceptibility genes for type 2 diabetes. In pancreatic beta-like cells differentiated from these lines, we found that mutations in CDKAL1, KCNQ1, and KCNJ11 led to impaired glucose secretion in vitro and in vivo, coinciding with defective glucose homeostasis. CDKAL1 mutant insulin+ cells were also hypersensitive to glucolipotoxicity. A high-content chemical screen identified a candidate drug that rescued CDKAL1-specific defects in vitro and in vivo by inhibiting the FOS/JUN pathway. Our approach of a proof-of-principle platform, which uses isogenic hESCs for functional evaluation of GWAS-identified loci and identification of a drug candidate that rescues gene-specific defects, paves the way for precision therapy of metabolic diseases.
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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.