Angelman syndrome-derived neurons display late onset of paternal UBE3A silencing

• DOI: 10.1038/srep30792
• Publication Date: 2016-08-03T09:32:48Z
• Authors: Jana Stanurova; Anika Neureiter; Michaela Hiber; Hannah de Oliveir...; Kristin Stolp; Roman Goetzke; Diana Klein; Agnes Bankfalvi; Hannes Klump; Laura Steenpass
• Keywords: Angelman Syndrome; UBE3A; Genomic Imprinting; Imprinting (psychology)

Abstract Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that regulated by a differentially methylated region. Gene mutations or failures the process lead to development of disorders, such as Angelman syndrome. The symptoms syndrome are caused absence functional UBE3A protein neurons brain. To create human neuronal model for syndrome, we reprogrammed dermal fibroblasts patient carrying defined three-base pair deletion into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental alleles present, distinguishable mutation and express . Detailed characterization iPSCs demonstrated their pluripotency exceptional stability region regulating imprinted expression. We observed strong induction SNHG14 silencing paternal only late during differentiation, vitro This new iPSC line allows study regulation on dissect molecular pathways affected protein.