Long non-coding RNAs in beta cell function

Considerable effort has been directed towards deciphering the molecular mechanisms that regulate β-cell formation, maturation and function. Past studies of pancreas development and β-cell function have largely focused on coding genes. In recent years, integrated analyses of islet-specific transcription factor binding sites, epigenetic modifications and gene expression profiles have uncovered the existence of chromatin domains and long non-coding RNAs (lncRNAs) with largely unknown functions. Notably, many of them are located in the genome nearby islet-specific genes, conserved across species and dynamically regulated by glucose concentration and throughout pancreas development. Although these features suggest a regulatory role in β-cell specification and function, few of them have been examined. The PI hypothesized that lncRNAs affect gene regulation in pancreas development and β-cell function. To test this hypothesis, he proposed to define the transcriptome profile of pancreatic lineages at single cell resolution using in vitro differentiation of human embryonic stem cells. Moreover, he will study the regulation and function of positionally-conserved lncRNAs in the specification of insulin-producing β-cells. The results from these studies will help generate alternative sources for β-cell replacement therapies.