Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader–Willi syndromes
| Autor: | Fouad Lemtiri-Chlieh, Stormy J. Chamberlain, Fany Bourgois-Rocha, Pin-Fang Chen, Marc Lalande, Khong Y. Ng, Eric S. Levine |
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| Rok vydání: | 2010 |
| Předmět: |
Pluripotent Stem Cells
congenital hereditary and neonatal diseases and abnormalities Ubiquitin-Protein Ligases Cellular differentiation Biology Models Biological Polymerase Chain Reaction Genomic Imprinting Angelman syndrome medicine UBE3A Humans Imprinting (psychology) Induced pluripotent stem cell DNA Primers Neurons Genetics Multidisciplinary nutritional and metabolic diseases Cell Differentiation Biological Sciences medicine.disease Immunohistochemistry nervous system diseases Electrophysiology DNA methylation Angelman Syndrome Genomic imprinting Prader-Willi Syndrome Reprogramming |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:17668-17673 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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