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. We identified 10 distinct cell types, annotated subpopulations of several cell types, and defined cell type-specific marker genes. We tested differential expression within each cell type across disease states and identified 1,701 genes with significant changes in expression, with most changes observed in ß-cells from donors with type 1 diabetes. To facilitate user interaction, we provide several single-cell visualization and reference mapping tools, as well as the open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology.

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. Here we present an integrated reference map of islet cell type-specific gene expression from 192,203 cells derived from single cell RNA-seq assays of 65 non-diabetic, T1D autoantibody positive (Aab+), T1D, and T2D donors from the Human Pancreas Analysis Program. We identified 10 endocrine and non-endocrine cell types as well as sub-populations of several cell types, and defined sets of marker genes for each cell type and sub-population. We tested for differential expression within each cell type in T1D Aab+, T1D, and T2D states, and identified 1,701 genes with significant changes in expression in any cell type. Most changes were observed in beta cells in T1D, and, by comparison, there were almost no genes with changes in T1D Aab+. To facilitate user interaction with this reference, we provide the data using several single cell visualization and reference mapping tools as well as open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology and diabetes.

CpG-creating mutations are costly in many human viruses.

Mutations can occur throughout the virus genome and may be beneficial, neutral or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly than similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are indeed costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses.