Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes

Consortia: CHIB, HPAC

Zhu H, Wang G, Nguyen-Ngoc KV, Kim D, Miller M, Goss G, Kovsky J, Harrington AR, Saunders DC, Hopkirk AL, Melton R, Powers AC, Preissl S, Spagnoli FM, Gaulton KJ, Sander M.
Dev Cell. 2023 Apr 3:S1534-5807(23)00107-7. doi: 10.1016/j.devcel.2023.03.011. Online ahead of print. PMID:37040771

All Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells m 6 A mRNA Methylation Regulates Early Pancreatic β-Cell Differentiation Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes Protein disorder in the regulatory control of mitophagy Human immune phenotyping reveals accelerated aging in type 1 diabetes Stromal Interaction Molecule 1 Maintains β Cell Identity and Function in Female Mice through Preservation of G Protein-Coupled Estrogen Receptor 1 Signaling The pathogenic “symphony” in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas Inferring regulators of cell identity in the human adult pancreas Generation of the NeoThy mouse model for human immune system studies GLP-1R agonists demonstrate potential to treat Wolfram syndrome in human preclinical models Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity Protocol to generate and utilize pancreatic tissue slices to study endocrine and exocrine physiology in situ from mouse and human tissue Major β cell-specific functions of NKX2.2 are mediated via the NK2-specific domain Human circulating and tissue-resident memory CD8(+) T cells Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes Pancreatic regional blood flow links the endocrine and exocrine diseases Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response Analysis of a macrophage carbamylated proteome reveals a function in post-translational modification crosstalk Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing Title: β Cell microRNAs Function as Molecular Hubs of Type 1 Diabetes Pathogenesis and as Biomarkers of Diabetes Risk Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells Acrylic-based culture plate format perfusion device to establish liver endothelial-epithelial interface cytoviewer: an R/Bioconductor package for interactive visualization and exploration of highly multiplexed imaging data m (6) A mRNA Methylation in Brown Adipose Tissue Regulates Systemic Insulin Sensitivity via an Inter-Organ Prostaglandin Signaling Axis Mapping genetic effects on cell type-specific chromatin accessibility and annotating complex immune trait variants using single nucleus ATAC-seq in peripheral blood Immune engineered extracellular vesicles to modulate T cell activation in the context of type 1 diabetes Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model Quantitative control of Ets1 dosage by a multi-enhancer hub promotes Th1 cell differentiation and protects from allergic inflammation Immunotherapy With Low-Dose IL-2/CD25 Prevents β-Cell Dysfunction and Dysglycemia in Prediabetic NOD Mice Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8(+) T cells A genomic data archive from the Network for Pancreatic Organ donors with Diabetes Integrating genetics with single-cell multiomic measurements across disease states identifies mechanisms of beta cell dysfunction in type 2 diabetes Senescence: a double-edged sword in beta-cell health and failure? 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