Abstract 18285: Embryonic Stem Cell Transcriptome Remodeling by a Nucleoporin Substrate for Atrial Fibrillation

Introduction: Nup155 is a nuclear pore complex protein identified as a potential clinical driver of idiopathic atrial fibrillation (Afib), however its mechanism of action is unknown. Here we examine effects of gene-trapped Nup155 haploinsufficiency (Nup155et) on an embryonic stem (ES) cell transcriptome prior to ES cell differentiation into cardiomyocyte-containing embryoid bodies. Methods: Nup155et ES cell lines (n=5) were cultured in parallel with wild type (WT) ES cells (n=5), total RNA was harvested for Illumina sequencing and analyzed using Strand NGS. Functional annotation and gene ontology enrichment were executed using DAVID and Ingenuity Pathways Analysis, and gene network analysis was performed using Cytoscape. Results: Transcriptome profiling of Nup155et and WT ES cells (A) depicted significant changes of 326 genes (176 upregulated and 150 downregulated genes) in the Nup155et group (B). These genes segregated into functional clusters within the up and downregulated sub-transcriptomes that enric...