Circulating pancreatic enzyme levels are a causal biomarker of type 1 diabetes.

Novel biomarkers of type 1 diabetes (T1D) are needed for earlier detection of disease and identifying therapeutic targets. We identified biomarkers of T1D by combining plasma and protein QTLs (pQTLs) for 2,922 proteins in the UK Biobank with a T1D genome-wide association study (GWAS) in 157k samples. T1D risk variants at over 20% of known loci colocalized with or pQTLs, and distinct sets of T1D loci colocalized with immune, pancreatic secretion, or gut-related proteins.

An Integrated Map of Cell Type-Specific Gene Expression in Pancreatic Islets.

Pancreatic islets consist of multiple cell types that produce hormones required for glucose homeostasis, and islet dysfunction is a major factor in type 1 and type 2 diabetes. Numerous studies have assessed transcription across individual cell types using single-cell assays; however, there is no canonical reference of gene expression in islet cell types that is also easily accessible for researchers to query and use in bioinformatics pipelines. Here we present an integrated map of islet cell type-specific gene expression from 192,203 cells from single-cell RNA sequencing of 65 donors without diabetes, donors who were type 1 diabetes autoantibody positive, donors with type 1 diabetes, and donors with type 2 diabetes from the Human Pancreas Analysis Program.

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

Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison.

An integrated map of cell type-specific gene expression in pancreatic islets.

Pancreatic islets are comprised of multiple endocrine cell types that produce hormones required for glucose homeostasis, and islet dysfunction is a major factor in the development of type 1 and type 2 diabetes (T1D, T2D). Numerous studies have generated gene expression profiles in individual islet cell types using single cell assays. However, there is no canonical reference of gene expression in islet cell types in both health and disease that is also easily accessible for researchers to access, query, and use in bioinformatics pipelines.

Characterization and Prevention of Hypovitaminosis C in Chimeric Mice with Humanized Livers.

Humanized liver chimeric mice (PXB-mice) are generated by the transplantation of human hepatocytes into mice that have severe combined immunodeficiency and express an albumin-promoted urokinase-type plasminogen activator (cDNA-uPA/SCID) transgene. Human hepatocytes cannot synthesize ascorbic acid (AA; commonly called vitamin C) and humans require supplementation to prevent vitamin C deficiency. PXB-mouse livers contain up to approximately 95% human hepatocytes, which likely affects AA synthesis.