UC Davis

During pancreatic development, insulin-producing beta cells, glucagon-producing alpha cells, and somatostatin-producing delta cells differentiate from a common endocrine progenitor. While these cells have been considered terminally differentiated, over the last several years it has become evident that pancreatic islet cellular identity is more plastic than previously appreciated. A cell?? ??an?c?i???me is the final outcome that stems from the interactions of both genomic and epigenomic components. Dynamic changes in chromatin accessibility alongside the recruitment of histone marks that either facilitate or repress gene transcription in tandem with transcription factor co-localization come together to define and maintain cellular identity through gene expression. Understanding of each of these components sheds further light on understanding cellular identity, with profiling the transcriptome providing signature patterns that are responsible for the functional behavior of these cells. Building on this through the interrogation of chromatin accessibility similarities and differences provides further insight into the mechanisms that govern cellular identity when coupled with the appropriate histone modification and transcription factor data. Ultimately, genomic and epigenomic characterizations of these major islet endocrine cell types can provide an avenue to further understanding the complex regulatory mechanisms that define and maintain cellular identity. Furthermore, these characterizations provide a resource for answering outstanding questions in the field.