An induced pluripotent stem cell model for ataxia telangiectasia
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ABSTRACT: 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. Three different cell types: fibroblasts, human embyronic stem cells, and induced pluripotent stem cells with heterozygote, homozygote A-T compared to normal samples.
ORGANISM(S): Homo sapiens
SUBMITTER: Othmar Korn
PROVIDER: E-GEOD-35347 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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