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| Status |
Public on May 28, 2012 |
| Title |
An induced pluripotent stem cell model for ataxia telangiectasia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The difficulty associated with generating induced pluripotent stem cells (iPSC) from patients with chromosomal instability syndromes suggests the cellular DNA damage response poses a barrier to reprogramming. Here we demonstrate that fibroblasts from patients with ataxia-telangiectasia (A-T) can be reprogrammed to bona-fide iPSC, albeit at a reduced efficiency. A-T iPSC display defective radiation-induced signaling, radiosensitivity and cell cycle checkpoint defects. Bioinformatic analysis of gene expression in the A-T iPSC identifies abnormalities in DNA damage signaling pathways as well as changes in mitochondrial and pentose phosphate pathways. A-T iPSC can be differentiated into functional neurons and thus represent a suitable model system to investigate A-T associated neurodegeneration. Collectively our data show that iPSC can be generated from a chromosomal instability syndrome and that these cells can be used to discover early developmental consequences of ATM deficiency, such as altered mitochondrial function, that may be relevant to A-T pathogenesis and amenable to therapeutic intervention.
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| Overall design |
Three different cell types: fibroblasts, human embyronic stem cells, and induced pluripotent stem cells with heterozygote, homozygote A-T compared to normal samples.
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| Contributor(s) |
Nayler S |
| Citation(s) |
23197857 |
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Sam Nayler, Magtouf Gatei, Sergei Kozlov, Richard Gatti, Jessica C. Mar, Christine A. Wells, Martin Lavin, and Ernst Wolvetang. 2012. Induced Pluripotent Stem Cells from Ataxia-Telangiectasia Recapitulate the Cellular Phenotype. Stem Cells Trans Med. Jul 1: 523 - 535. doi: 10.5966/sctm.2012-0024
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| Submission date |
Jan 25, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Othmar Korn |
| Organization name |
Australian Institute for Bioengineering and Nanotechnology
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| Street address |
University of Queensland
|
| City |
St. Lucia |
| State/province |
Queensland |
| ZIP/Postal code |
4067 |
| Country |
Australia |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA152721 |
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