Project Abstracts - HPAC

Mark Atkinson, PhD, Investigator, University of Florida
Marcela Brissova, PhD, co-Investigator, Vanderbilt University
Mingder Yang, PhD, co-Investigator, University of Florida
Irina Kusmartseva, PhD, co-Investigator, University of Florida

Start Date: September 20, 2016
End Date: August 31, 2021

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Abstract

The Integrated Program for Human Pancreas Analysis at Vanderbilt University and the University of Florida (UC4 DK112232) is working collaboratively with the University of Pennsylvania (UC4 DK112217) to increase our understanding key aspects of human type 1 diabetes (T1D) pathogenesis, especially the molecular events in the pancreas and islets. Investigators in the Florida and Vanderbilt groups are using infrastructure and expertise to identify human pancreata from individuals with new-onset T1D or at high-risk for T1D. The groups at the University of Pennsylvania, Vanderbilt, and Florida are collecting and phenotyping the pancreas and islets using new and emerging technologies to generate new knowledge, resources, and datasets that will be made available to HIRN investigators and scientists interested in T1D. In 2021, the research groups integrated into one formal grant (UC4 DK112217) to continue efforts on this project. 

Publications

• Sex-specific regulatory architecture of pancreatic islets from subjects with and without type 2 diabetes
• Human peripancreatic adipose tissue paracrine signaling impacts insulin secretion, blood flow, and gene transcription
• HumanIslets.com: Improving accessibility, integration, and usability of human research islet data
• Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
• Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk
• Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners
• No evidence for persistent enteroviral B infection of pancreatic islets in type 1 diabetic and pre-diabetic patients from RNA-Seq data
• Identification of unique cell type responses in pancreatic islets to stress
• HumanIslets: An integrated platform for human islet data access and analysis
• AnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics
• DNA methylation-based assessment of cell composition in human pancreas and islets
• RFX6 maintains gene expression and function of adult human islet α cells
• Genetic risk converges on regulatory networks mediating early type 2 diabetes
• Human Pseudoislet System for Synchronous Assessment of Fluorescent Biosensor Dynamics and Hormone Secretory Profiles
• Exocrine pancreas in type 1 and type 2 diabetes: different patterns of fibrosis, metaplasia, angiopathy, and adiposity
• Benchmarking algorithms for joint integration of unpaired and paired single-cell RNA-seq and ATAC-seq data
• The leptin receptor has no role in delta-cell control of beta-cell function in the mouse
• Pancreatic islet α cell function and proliferation requires the arginine transporter SLC7A2
• An Integrated Map of Cell Type-Specific Gene Expression in Pancreatic Islets
• Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes
• Inferring regulators of cell identity in the human adult pancreas
• Integrating genetics with single-cell multiomic measurements across disease states identifies mechanisms of beta cell dysfunction in type 2 diabetes
• An integrated map of cell type-specific gene expression in pancreatic islets
• Human pancreatic capillaries and nerve fibers persist in type 1 diabetes despite beta cell loss
• Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes
• Understanding islet dysfunction in type 2 diabetes through multidimensional pancreatic phenotyping: The Human Pancreas Analysis Program
• Aging compromises human islet beta cell function and identity by decreasing transcription factor activity and inducing ER stress
• Every islet matters: improving the impact of human islet research
• Adaptation to chronic ER stress enforces pancreatic β-cell plasticity
• α Cell dysfunction in islets from nondiabetic, glutamic acid decarboxylase autoantibody-positive individuals
• Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits
• Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state
• Islet Lymphocytes Maintain a Stable Regulatory Phenotype Under Homeostatic Conditions and Metabolic Stress
• RFX6-mediated dysregulation defines human β cell dysfunction in early type 2 diabetes
• Microvessels enhance vascularization and function of transplanted insulin-producing cells
• Integrated Analysis of the Pancreas and Islets Reveals Unexpected Findings in Human Male With Type 1 Diabetes
• Combinatorial transcription factor profiles predict mature and functional human islet α and β cells
• What is a β cell? – Chapter I in the Human Islet Research Network (HIRN) Review Series
• Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass
• A New Hypothesis for Type 1 Diabetes Risk: The At-Risk Allele at rs3842753 Associates With Increased Beta-cell INS Messenger RNA in a Meta-Analysis of Single-Cell RNA-Sequencing Data
• The Human Islet: Mini-organ with Mega-impact
• Type 1 diabetes mellitus: much progress, many opportunities
• Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets
• Pancreatic islet reserve in type 1 diabetes
• RIPK3-mediated inflammation is a conserved β cell response to ER stress
• SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells
• Pancreatlas: Applying an Adaptable Framework to Map the Human Pancreas in Health and Disease
• Single cell transcriptomics of human islet ontogeny defines the molecular basis of β cell dedifferentiation in T2D
• Dapagliflozin does not directly affect human α or β cells
• Decreased pancreatic acinar cell number in type 1 diabetes
• Integrated human pseudoislet system and microfluidic platform demonstrates differences in G-protein-coupled-receptor signaling in islet cells
• High throughput pMHC-I tetramer library production using chaperone-mediated peptide exchange
• Tacrolimus- and sirolimus-induced human β cell dysfunction is reversible and preventable
• Lipid Droplet Accumulation in Human Pancreatic Islets is Dependent Upon Both Donor Age and Health
• Modeling Monogenic Diabetes using Human ESCs Reveals Developmental and Metabolic Deficiencies Caused by Mutations in HNF1A
• NIH Initiative to Improve Understanding of the Pancreas, Islet, and Autoimmunity in Type 1 Diabetes: The Human Pancreas Analysis Program (HPAP)
• Imaging mass spectrometry enables molecular profiling of mouse and human pancreatic tissue
• HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of islet β-Cells from Donors with Type 1 Diabetes
• Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes
• Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis
• Cystic fibrosis-related diabetes is caused by islet loss and inflammation
• α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes