Type 1 diabetes (T1D) is an autoimmune disorder that affects 1.25 million individuals in the US and for which there is no known cause or cure. T1D is characterized by autoimmune destruction of insulin- producing beta cells in the pancreatic islets. The pancreas consists of multiple different cell-types relevant to diabetes pathogenesis including endocrine (beta, alpha, delta, gamma, and epsilon), exocrine (ductal and acinar), immune (macrophage, dendritic, T cells, and others), and endothelial cells. In addition, there is evidence for further cellular heterogeneity within individual cell types. Each cell- type has distinct functions in pancreas biology, yet the complete repertoire of pancreatic cell-types in non-diabetic and diabetic individuals, and the regulatory programs that define their identity and their roles in diabetes pathogenesis are unknown. Technological advances have enabled profiling chromatin and gene expression in individual cells which can reveal regulatory programs in specific cell types to facilitate understanding their role in disease. For this project we will adapt cutting edge single-cell methods on nPOD frozen samples from non-diabetic and diabetic donors to define cell-types and identify mechanisms of disease promoting cross-talk between cells.