Single-Cell Epigenomics of Pancreatic Islets

The pancreatic islet contains multiple interacting cell types (beta, alpha, delta, and others), each with distinct transcriptional programs and disease associations. My PhD work applied single-cell ATAC-seq to human islets to generate high-resolution maps of cell-type-specific chromatin accessibility, revealing regulatory programs active in each cell type 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.