title: Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes.
abstract: Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are neurodevelopmental disorders of genomic imprinting. AS results from loss of function of the ubiquitin protein ligase E3A (UBE3A) gene, whereas the genetic defect in PWS is unknown. Although induced pluripotent stem cells (iPSCs) provide invaluable models of human disease, nuclear reprogramming could limit the usefulness of iPSCs from patients who have AS and PWS should the genomic imprint marks be disturbed by the epigenetic reprogramming process. Our iPSCs derived from patients with AS and PWS show no evidence of DNA methylation imprint erasure at the cis-acting PSW imprinting center. Importantly, we find that, as in normal brain, imprinting of UBE3A is established during neuronal differentiation of AS iPSCs, with the paternal UBE3A allele repressed concomitant with up-regulation of the UBE3A antisense transcript. These iPSC models of genomic imprinting disorders will facilitate investigation of the AS and PWS disease processes and allow study of the developmental timing and mechanism of UBE3A repression in human neurons.
authors.affiliation: University of Connecticut Stem Cell Institute and Departments of Genetics and Developmental Biology and Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA. chamberlain@uchc.edu
authors.forename: Stormy J
authors.initials: SJ
authors.lastname: Chamberlain
authors.forename: Pin-Fang
authors.initials: PF
authors.lastname: Chen
authors.forename: Khong Y
authors.initials: KY
authors.lastname: Ng
authors.forename: Fany
authors.initials: F
authors.lastname: Bourgois-Rocha
authors.forename: Fouad
authors.initials: F
authors.lastname: Lemtiri-Chlieh
authors.forename: Eric S
authors.initials: ES
authors.lastname: Levine
authors.forename: Marc
authors.initials: M
authors.lastname: Lalande
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004594:Electrophysiology; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D009474:Neurons / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011218:Prader-Willi Syndrome / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D017931:DNA Primers; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases