ArticleNature genetics2023
Integrating genetics with single-cell multiomic measurements across disease states identifies mechanisms of beta cell dysfunction in type 2 diabetes.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 72 citations in OpenAlex.
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.Life science alliance · 2026Article
- Disentangling covariate effects on single-cell-resolved epigenomes with DeepDive.Patterns (New York, N.Y.) · 2026Article
- What-if effects: A tale of entangled covariates.Patterns (New York, N.Y.) · 2026Article
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Mapping enhancer-gene regulatory interactions from single-cell data.Nature genetics · 2026Article
- Distinct macrophage and T cell programs shape pancreatic inflammation during metabolic stress and aging.bioRxiv : the preprint server for biology · 2026Article
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Supervised machine learning identifies impaired mitochondrial quality control in β-cells with development of type 2 diabetes.NPJ systems biology and applications · 2026Article
- Workload-induced changes to cell state contribute to β-cell failure in diabetes.bioRxiv : the preprint server for biology · 2026Article
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.Nature communications · 2026Article
- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 2026Article
- Nanopore Electroporation: A New Delivery Method Within the Field of Epigenetic Editing.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.Nature metabolism · 2026Article
- pertTF: context-aware AI modeling for genome-scale and cross-system perturbation prediction.bioRxiv : the preprint server for biology · 2026Article
- Systematic evaluation of single-cell multimodal data integration enhances cell type resolution and discovery of clinically relevant states in complex tissues.Genome biology · 2026Article
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes.Nature medicine · 2026Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
Dysfunctional pancreatic islet beta cells are a hallmark of type 2 diabetes (T2D), but a comprehensive understanding of the underlying mechanisms, including gene dysregulation, is lacking. Here we integrate information from measurements of chromatin accessibility, gene expression and function in single beta cells with genetic association data to nominate disease-causal gene regulatory changes in T2D. Using machine learning on chromatin accessibility data from 34 nondiabetic, pre-T2D and T2D donors, we identify two transcriptionally and functionally distinct beta cell subtypes that undergo an abundance shift during T2D progression. Subtype-defining accessible chromatin is enriched for T2D risk variants, suggesting a causal contribution of subtype identity to T2D. Both beta cell subtypes exhibit activation of a stress-response transcriptional program and functional impairment in T2D, which is probably induced by the T2D-associated metabolic environment. Our findings demonstrate the power of multimodal single-cell measurements combined with machine learning for characterizing mechanisms of complex diseases.
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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.