Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes.
Proc Natl Acad Sci U S A
; 107(41): 17668-73, 2010 Oct 12.
Article
em En
| MEDLINE
| ID: mdl-20876107
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.
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Prader-Willi
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Diferenciação Celular
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Síndrome de Angelman
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Impressão Genômica
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Células-Tronco Pluripotentes
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Modelos Biológicos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article