PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development

Consortia: CTAR

Lau HH, Krentz NAJ, Abaitua F, Perez-Alcantara M, Chan JW, Ajeian J, Ghosh S, Lee Y, Yang J, Thaman S, Champon B, Sun H, Jha A, Hoon S, Tan NS, Gardner DS, Kao SL, Tai ES, Gloyn AL, Teo AKK. Nat Commun. 2023 Sep 30;14(1):6119. doi: 10.1038/s41467-023-41860-z. PMID: 37777536

Published Works 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 Supervised machine learning identifies impaired mitochondrial quality control in β cells with development of type 2 diabetes Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells Microvascular Homeostasis Is Compromised in Pancreatic Islets in a Mouse Model of β-Cell Loss and Low-Grade Inflammation 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 Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression Chimeric anti-HLA antibody receptor engineered human regulatory T cells suppress alloantigen-specific B cells from pre-sensitized transplant recipients Proteogenomic Discovery of Novel Open Reading Frames With HLA Immune Presentation on Human β-Cells Coxsackievirus B infection invokes unique cell-type-specific responses in primary human pancreatic islets A neural entero-pancreatic pathway that regulates insulin secretion and glucose tolerance Proinflammatory Stress Activates Neutral Sphingomyelinase 2-Based Generation of a Ceramide-Enriched β-Cell EV Subpopulation A vascular-associated fibroblastic cell controls pancreatic islet immunity Autoimmune diabetes and targets for immunomodulation Beta cell dysfunction occurs independently of insulitis in type 1 diabetes pathogenesis Protein carbamylation and proteomics: from artifacts to elucidation of biological functions Histopathology-based protein multiplex generation using deep learning The integrated stress response promotes macrophage inflammation and migration in autoimmune diabetes Increased longevity of circulating human IgG in an NSG Fc gamma receptor-1 deficient humanized mouse model Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy Divergent Cell-Type Specific Hypoxia Responses in Human Stem Cell-Derived and Primary Islets Spatially Bound Functional Heterogeneity Drives Modular Organization in Beta Cell Networks Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes The pathophysiology, presentation and classification of Type 1 diabetes The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals Loss of Insulin-Positive Cell Clusters Precedes the Decrease in Islet Frequency and β-Cell Area in Type 1 Diabetes LONP1 loss causes mitochondrial mayhem in β-cells The antigen presentation landscape of cytokine-stressed human pancreatic islets A structure-guided approach to predict MHC-I restriction of T cell receptors for public antigens Exendin-4 enhances insulin-positive phenotype of human pluripotent stem cell-derived β cells during transplantation OLIVE Provides Rapid Visualization and Analysis of Chromatin Tracing Experiments Inference of multi-enhancer interactions in T lymphocytes using Hi-Cociety Improved conditioning for hematopoietic chimerism induces islet tolerance to cure diabetes Small molecule modulators of TOX protein re-invigorate T cell activity Scalable 3D Bioprinting of Human Islets in a Pancreatic Decellularized Extracellular Matrix-Enriched Bioink for Beta-Cell Replacement Therapy Streamlining Multiplexed Tissue Image Analysis with PIPΣX: An Integrated Automated Pipeline for Image Processing and EXploration for Diverse Tissue Types Ultrasmall chemogenetic tags with group-transfer ligands Microvascular homeostasis is compromised in pancreatic islets in a mouse model of beta cell loss and low-grade inflammation Challenges and Opportunities for Understanding the Pathogenesis of Type 1 Diabetes: An Endocrine Society Scientific Statement Epigenetic adaptation of beta cells across lifespan and disease: age-related demethylation is advanced in type 2 diabetes Pancreatic β-cell regeneration in situ by the ALK3 agonist THR-123 Spatial patterns of hepatocyte glucose flux revealed by stable isotope tracing and multi-scale microscopy
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Email: hirnec@coh.org