Single-Cell Epigenomics of Pancreatic Islets

Hundreds of genetic variants influence type 2 diabetes risk, but most sit in non-coding regions of the genome where their function is invisible without cell-type-specific regulatory maps. My PhD work applied single-cell ATAC-seq to human islets to generate high-resolution maps of chromatin accessibility in each cell type (beta, alpha, delta, and others), revealing which regulatory programs are active in each and linking them to type 2 diabetes GWAS loci (Chiou* et al., 2021). This provided a framework for interpreting non-coding genetic variants in the context of islet cell-type identity.

Complementary work characterized how environmental and nutrient signals reshape the islet epigenome to control adaptive insulin secretion (Wortham et al., 2023), and examined how genetic variation at type 2 diabetes loci affects cell-type-specific regulatory activity across disease states (Wang* et al., 2023). The resulting resource, a catalog of islet cell-type regulatory elements annotated with disease-relevant variants, is widely used in the field for interpreting diabetes GWAS results.

Related: Type 1 Diabetes and the Exocrine Pancreas — companion project revealing acinar cell contributions to T1D genetic risk using the same single-cell epigenomic approach.