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Increased X-ray sensitivity and sustained chromosomal stability in Ataxia Telangiectasia-derived induced pluripotent stem (AT-iPS) cells

ABSTRACT: Disease-specific induced pluripotent stem (iPS) cells have been used for a model to analyze pathogenesis of the disease. In this study, we generated iPS cells derived from a fibroblastic cell line of ataxia telangiectasia (AT-iPS cells), a neurodegenerative, inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. AT-iPS cells exhibited hypersensitivity to X-ray irradiation, one of the characteristics of the disease. Surprisingly, while parental ataxia telangiectasia cells exhibited significant chromosomal abnormalities, AT-iPS cells did not show any chromosomal instability in vitro, i.e. maintenance of intact chromosomes at least by 80 passages (560 days) probably due to robust stability of pluripotent stem cells such as iPS cells and embryonic stem cells. The whole exome analysis also showed comparable nucleotide substitution speed in AT-iPS cells. Interestingly, after longer period of AT-iPS implantation into immunodeficient mice, teratoma generated by AT-iPS cells exhibited telangiectasia and carcinogenesis that are two characteristic symptoms of ataxia telangiectasia. Taken together, AT-iPS cells would be a good model for ataxia telangiectasia to clarify pathogenesis of the disease, and may allow us to facilitate development of drugs that inhibit ataxia and hypersensitivity to ionizing radiation for therapeutic application. The parental AT1OS fibroblast cells and four independent AT-iPS clones were subjected to Illumina HumanCytoSNP-12 v2.1 BeadChip analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Akihiro Umezawa

PROVIDER: E-GEOD-47498 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Increased X-ray sensitivity and sustained chromosomal stability in Ataxia Telangiectasia-derived induced pluripotent stem (AT-iPS) cells

Project description:Disease-specific induced pluripotent stem (iPS) cells have been used for a model to analyze pathogenesis of the disease. In this study, we generated iPS cells derived from a fibroblastic cell line of ataxia telangiectasia (AT-iPS cells), a neurodegenerative, inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. AT-iPS cells exhibited hypersensitivity to X-ray irradiation, one of the characteristics of the disease. Surprisingly, while parental ataxia telangiectasia cells exhibited significant chromosomal abnormalities, AT-iPS cells did not show any chromosomal instability in vitro, i.e. maintenance of intact chromosomes at least by 80 passages (560 days) probably due to robust stability of pluripotent stem cells such as iPS cells and embryonic stem cells. The whole exome analysis also showed comparable nucleotide substitution speed in AT-iPS cells. Interestingly, after longer period of AT-iPS implantation into immunodeficient mice, teratoma generated by AT-iPS cells exhibited telangiectasia and carcinogenesis that are two characteristic symptoms of ataxia telangiectasia. Taken together, AT-iPS cells would be a good model for ataxia telangiectasia to clarify pathogenesis of the disease, and may allow us to facilitate development of drugs that inhibit ataxia and hypersensitivity to ionizing radiation for therapeutic application.

2013-06-22 | GSE47498 | GEO

Genomic alteration in MRC5-derived induced pluripotent stem (MRC5-iPS) cell line, Tic

Project description:Disease-specific induced pluripotent stem (iPS) cells have been used for a model to analyze pathogenesis of the disease. We generated iPS cells derived from a fibroblastic cell line of ataxia telangiectasia (AT-iPS cells). In analysis of AT-iPS cells, the human wild-type iPS cell line (MRC5-iPS) was generated and cultured in the same conditions as the diseased iPS cell lines. It is an ideal control cell line for the disease and patient-specific iPS cell lines. Because MRC5-iPS cells exhibited considerable chromosomal abnormalities in vitro, we performed a structural alteration analysis by using a SNP genotyping array for MRC5-iPS cell line, Tic, at passage 15, passage 30, and passage 37.

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Genomic alteration in MRC5-derived induced pluripotent stem (MRC5-iPS) cell line, Tic

2013-07-23 | E-GEOD-49082 | biostudies-arrayexpress

NSMF promotes the replication stress-induced DNA damage response for genome maintenance

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Restoration of defective nuclear-mitochondrial DNA damage signaling suppresses neuropathology and extends healthspan in Ataxia telangiectasia across species

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Reduced phosphorylated ATM expression is associated with poor prognosis and gemcitabine resistance in pancreatic cancer

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ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts

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ATM regulates a DNA damage response post-transcriptional RNA operon in lymphocytes

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2011-01-05 | GSE25848 | GEO

Homo sapiens

Project description:Increased X-ray sensitivity and sustained chromosomal stability in Ataxia Telangiectasia-derived induced pluripotent stem (AT-iPS) cells

| PRJNA205892 | ENA

ATM regulates a DNA damage response post-transcriptional RNA operon in lymphocytes

2011-01-05 | E-GEOD-25848 | biostudies-arrayexpress