Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes

Stormy J. Chamberlain, Pin Fang Chen, Khong Y. Ng, Fany Bourgois-Rocha, Fouad Lemtiri-Chlieh, Eric S. Levine, Marc Lalande

Research output: Contribution to journalArticlepeer-review

229 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17668-17673
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number41
DOIs
StatePublished - Oct 12 2010

Keywords

  • Antisense transcript
  • Epigenetic
  • Neuronal differentiation

ASJC Scopus subject areas

  • General

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