Epigenetic adaptation of beta cells across lifespan and disease

Consortia: HPAC

Manduchi E, Descamps HC, Liu J, Schug J, Da T, Lahori D, El-Mekkoussi H, Lee M, Feleke E, Bernstein D, Liu C, Naji A, Glaser B, Kaestner KH, Avrahami D.
Nat Metab. 2026 Apr;8(4):941-956. doi: 10.1038/s42255-026-01495-y. Epub 2026 Apr 24. PMID:42032110

Published Works Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes Applications of Stem Cell-Derived Islets and Emerging Experimental Platforms to Understand Diabetes Dissecting human organ development using spatial technologies AutoPCR: automated phenotype concept recognition by prompting Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata Mapping histologic and functional maturation of human endocrine pancreas across early postnatal periods Assessing Extracellular Vesicle Proteins as Predictive Biomarkers for Developing Type 1 Diabetes Optimizing post-transplantation detection of subcutaneously transplanted islets using dithizone staining Real-time in vivo analysis of murine β cells reveals autophagic flux defects before onset of autoimmune diabetes A mitochondrial ROS-dependent antiviral response promotes β cell resilience and is diminished in donors with type 1 diabetes Supervised machine learning identifies impaired mitochondrial quality control in β-cells with development of type 2 diabetes New and emerging therapies in type 1 diabetes mellitus Accounting for Age-Related Increases in HbA1c More Accurately Quantifies Risk of Type 1 Diabetes Progression in Islet Autoantibody-Positive Adults Differential Contributions of IgM and IgG Autoantibodies to Serologic IA2 Reactivity in Type 1 Diabetes Epigenetic adaptation of beta cells across lifespan and disease Beta cell microRNAs function as molecular hubs of type 1 diabetes pathogenesis and as biomarkers of diabetes risk Whole-genome CRISPR screening identifies genetic modifiers of stem cell-derived islet transplantation Spatial transcriptomics from pancreas and local draining lymph node tissue reveals a lymphotoxin-β signature in human type 1 diabetes Enhanced hypoxia resistance distinguishes human pluripotent stem cell-derived islets from primary islets Paracrine inhibition via G protein inwardly rectifying potassium channels regulates glucagon secretion from human pancreatic alpha cells Islet-derived T cells from both mice and humans recognize conserved insulin A-chain peptides presented by HLA-C*03:04 Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles Lysine Targeting Group-Transfer Chimeras for Proximity Induction Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes BRD4 Phosphorylation Regulates the Structure of Chromatin Nanodomains Longitudinal monitoring of type 1 diabetes progression to disease onset Optimizing Single-Cell Long-Read Sequencing for Enhanced Isoform Detection in Pancreatic Islets Baseline Insulin Secretion Determines Response to Abatacept in Stage 1 Type 1 Diabetes Persistent urinary metabolic signatures in children with type 1 diabetes Activating Muscarinic Receptor Signaling in Intrapancreatic Neurons Is Required for Parasympathetic Cholinergic Control of Pancreatic Cell Function DEC1 regulates human β cell functional maturation and circadian rhythm Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells ADAR1 editing is necessary for only a small subset of cytosolic dsRNAs to evade MDA5-mediated autoimmunity CelLink: integrating single-cell multi-omics data with weak feature linkage and imbalanced cell populations Compressed sensing expands the multiplexity of imaging mass cytometry Developing a general AI model for integrating diverse genomic modalities and comprehensive genomic knowledge Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices Long-term culture of human pancreatic islets reveals reduced metal ion pathways in their gene signature Joint profiling of gene expression and chromatin accessibility in pancreatic lymph nodes and spleens in human type 1 diabetes Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells Curing autoimmune diabetes in mice with islet and hematopoietic cell transplantation after CD117 antibody-based conditioning A web tool for easy and versatile analysis of human endocrine pancreas single-cell RNAseq data Microvascular Homeostasis Is Compromised in Pancreatic Islets in a Mouse Model of β-Cell Loss and Low-Grade Inflammation Beta cell secreted GABA sets appropriate insulin secretion by modulating islet calcium oscillations Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and Parkin-independent mitophagy Human NKX2.2 influences islet endocrine cell fate choices through regulation of WNT pathway genes Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes Challenges and Opportunities in State-of-the-Art Proteomics Analysis for Biomarker Development From Plasma Extracellular Vesicles
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