RNA-Seq to identify genes regulated by NFATc2 expression in islet stress response and function

The downstream CN target NFATc2 is highest among enriched regulators of top induced genes in human islets exposed to high glucose and IL-1β. Thus, we used a conditional transgenic β-cell specific NFATc2 knock out (NFATc2βKO) mouse model to analyze requirements of NFATc2 to regulate genes in response to metabolic and inflammatory stress. Transcript analysis of NFATc2βKO islets exposed to high glucose and IL-1β revealed NFATc2-dependent downregulation of genes known to promote β-cell differentiation and upregulation of β-cell disallowed genes. Collectively, these results suggest that CN/NFATc2 signaling is required for expression of genes that maintain β cells in a differentiated state, and its inactivation allows genome-wide transcriptional changes that promote β-cell dedifferentiation when exposed to metabolic and inflammatory stress. islets were isolated from two wildtype and two NFATc2βKO mice. Islets from each mouse were either untreated or subjected to high glucose and cytokine cocktail for 2 hr. All treatments and knockout mice samples were compared to wildtype controls.