Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of human olfactory neurosphere derived (ONS) cells to investigate a patient-specific olfactory stem cell disease model for ataxia-telangiectasia.

ABSTRACT: Nasal biopsies were collected from control and A-T patients prior to establishing olfactory neurosphere derived (ONS) cells. These cells were phenotyped using stem cell markers, a series of A-T cellular characteristics determined and cells differentiated into neuronal cells.

ORGANISM(S): Homo sapiens

DISEASE(S): normal

SUBMITTER: Nicholas Matigian

PROVIDER: E-MTAB-1217 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A patient-derived olfactory stem cell disease model for ataxia-telangiectasia.

Stewart Romal R Kozlov Sergei S Matigian Nicholas N Wali Gautam G Gatei Magtouf M Sutharsan Ratneswary R Bellette Bernadette B Wraith-Kijas Amanda A Cochrane Julie J Coulthard Mark M Perry Chris C Sinclair Kate K Mackay-Sim Alan A Lavin Martin F MF

Human molecular genetics 20130307 12

The autosomal recessive disorder ataxia-telangiectasia (A-T) is characterized by genome instability, cancer predisposition and neurodegeneration. Although the role of ataxia-telangiectasia mutated (ATM) protein, the protein defective in this syndrome, is well described in the response to DNA damage, its role in protecting the nervous system is less clear. We describe the establishment and characterization of patient-specific stem cells that have the potential to address this shortcoming. Olfacto ...[more]

PMID: 23474819

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Project description:Epigenetics describes mechanisms via which the environment can act on the genome, including DNA methylation of promoter regions of genes. This could be a way that environmental risk factors could affect neurodevelopment in individuals at risk for schizophrenia. Patient-derived cells provide a means whereby epigenetics and gene-environment interactions might be investigated. Induced pluripotent stem cells (iPS cells) present an attractive patient-derived cellular model because they can be differentiated into cell types of interest in schizophrenia. In this study the influence of the reprogramming process on schizophrenia-associated DNA methylation was investigated through genome-wide DNA methylation profiling and gene expression of patient-derived iPS cells and the fibroblasts from which they were derived. Olfactory neurosphere-derived cells (ONS cells) from the same patients were also profiled to provide a window on epigenetic regulation in three distinct cell types. Patient-derived cell were compared to cells derived from healthy controls to identify differences in DNA methylation and gene expression associated with schizophrenia in three cell types. The main finding is that iPS cells, prior to neuronal differentiation, demonstrated significant schizophrenia-associated differences in DNA methylation. This is in contrast to the fibroblasts from which they were derived, which show lesser schizophrenia-associated differences in DNA methylation. Like iPS cells, ONS cells showed robust significant schizophrenia-associated differences in DNA methylation. Notably, the schizophrenia-associated differences in DNA methylation were unique for each cell type, with little overlap between them, and only 5 genes commonly methylated in all cell types. Gene expression differences among the cell types mirrored the DNA methylation differences in magnitude, again with little overlap in specific genes affected. Gene Ontology analysis of the affected genes identified common cellular process affected in all three cell types without the same genes contributing. These data suggest that most DNA methylation differences are driven by the demands imposed by each cell type with schizophrenia-associated differences also being cell-type specific. Thus DNA methylation may not be a cause of schizophrenia-associated differences in cell functions in these cells but rather a downstream consequence of some unidentified causative mechanisms. This dataset represents the DNA methylation part of the study. The gene expression data is deposited under accession E-MTAB-5016.

Dataset Information

Transcription profiling by array of human olfactory neurosphere derived (ONS) cells to investigate a patient-specific olfactory stem cell disease model for ataxia-telangiectasia.

Publications

A patient-derived olfactory stem cell disease model for ataxia-telangiectasia.

Similar Datasets

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