Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

HEK293lines_Human_Exon_1.0_ST_arrays_exondata

ABSTRACT: Comparison of transcriptional profiles of 6 different HEK293 cell line variants, at the exon-level (extended set) and gene-level (core set)

ORGANISM(S): Homo sapiens

SUBMITTER: Morgane Boone

PROVIDER: E-MEXP-3516 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations.

Lin Yao-Cheng YC Boone Morgane M Meuris Leander L Lemmens Irma I Van Roy Nadine N Soete Arne A Reumers Joke J Moisse Matthieu M Plaisance Stéphane S Drmanac Radoje R Chen Jason J Speleman Frank F Lambrechts Diether D Van de Peer Yves Y Tavernier Jan J Callewaert Nico N

Nature communications 20140903

The HEK293 human cell lineage is widely used in cell biology and biotechnology. Here we use whole-genome resequencing of six 293 cell lines to study the dynamics of this aneuploid genome in response to the manipulations used to generate common 293 cell derivatives, such as transformation and stable clone generation (293T); suspension growth adaptation (293S); and cytotoxic lectin selection (293SG). Remarkably, we observe that copy number alteration detection could identify the genomic region tha ...[more]

PMID: 25182477

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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

HEK293lines_Human_Exon_1.0_ST_arrays_exondata

Publications

Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations.

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