Untangling the genetics of beta cell dysfunction and death in type 1 diabetes

Consortia: CBDS, CTAR, HIREC, Opportunity Pool Projects

Robertson CC, Elgamal RM, Henry-Kanarek BA, Arvan P, Chen S, Dhawan S, Eizirik DL, Kaddis JS, Vahedi G, Parker SCJ, Gaulton KJ, Soleimanpour SA.
Mol Metab. 2024 Aug;86:101973. doi: 10.1016/j.molmet.2024.101973. Epub 2024 Jun 22. PMID:38914291

All Increased Inflammation as well as Decreased Endoplasmic Reticulum Stress and Translation Differentiate Pancreatic Islets of Pre-symptomatic Stage 1 Type 1 Diabetes and Non-diabetic Cases Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset Role of Sec61α2 translocon in insulin biosynthesis m(6)A mRNA methylation by METTL14 regulates early pancreatic cell differentiation Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms RNA Splicing Events in Circulation Distinguish Individuals with and without New-Onset Type 1 Diabetes m(6)A mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1 Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead Limitations in mitochondrial programming restrain the differentiation and maturation of human stem cell-derived β cells CNTools: A computational toolbox for cellular neighborhood analysis from multiplexed images Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements Sodium butyrate prevents cytokine-induced β-cell dysfunction through restoration of stromal interaction molecule 1 expression and activation of store-operated calcium entry 12-Lipoxygenase inhibition suppresses islet immune and inflammatory responses and delays autoimmune diabetes in human gene replacement mice No evidence for persistent enteroviral B infection of pancreatic islets in type 1 diabetic and pre-diabetic patients from RNA-Seq data Diabetes mellitus-Progress and opportunities in the evolving epidemic Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic β-cells CD39 delineates chimeric antigen receptor regulatory T cell subsets with distinct cytotoxic & regulatory functions against human islets Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 h Identification of unique cell type responses in pancreatic islets to stress The Chicken or the Egg Dilemma: Understanding the Interplay between the Immune System and the β Cell in Type 1 Diabetes HumanIslets: An integrated platform for human islet data access and analysis A metabolic redox relay supports ER proinsulin export in pancreatic islet β-cells Untangling the genetics of beta cell dysfunction and death in type 1 diabetes Beta cell dedifferentiation in type 1 diabetes: sacrificing function for survival? LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes Inhibition of the eukaryotic initiation factor-2-α kinase PERK decreases risk of autoimmune diabetes in mice Enhancing Therapeutic Insulin Transport from Macroencapsulated Islets Using Sub-Minute Pressure at Physiological Levels Roadblocks confronting widespread dissemination and deployment of Organs on Chips AAV Capsid Screening for Translational Pig Research Using a Mouse Xenograft Liver Model Do We Need a New Hypothesis for KATP Closure in β-Cells? Distinguishing the Baby From the Bathwater Unfolding emergency calls stress granules to the ER Immuno-Scanning Electron Microscopy of Islet Primary Cilia Human insulin as both antigen and protector in type 1 diabetes A Golden Hour and Golden Opportunity for β-Cell Preservation The integrated stress response in pancreatic development, tissue homeostasis, and cancer Network approach reveals preferential T-cell and macrophage association with α-linked β-cells in early stage of insulitis in NOD mice Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice Physiomimetic Fluidic Culture Platform on Microwell-Patterned Porous Collagen Scaffold for Human Pancreatic Islets Data-driven selection of analysis decisions in single-cell RNA-seq trajectory inference AnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics CD4+ T Cells From Individuals With Type 1 Diabetes Respond to a Novel Class of Deamidated Peptides Formed in Pancreatic Islets Senescence of human pancreatic beta cells enhances functional maturation through chromatin reorganization and promotes interferon responsiveness Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets Proinflammatory stress activates neutral sphingomyelinase 2 based generation of a ceramide-enriched β cell EV subpopulation De novo identification of CD4(+) T cell epitopes Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes
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Email: hirnec@coh.org