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E-GEOD-30653 - Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina Infinium 27K DNA Methylation]

Status
Released on 13 May 2012, last updated on 25 June 2012
Organism
Homo sapiens
Samples (283)
Array (1)
Protocols (6)
Description
Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting, and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting. To obtain a comprehensive view of hPSC-specific epigenomic patterns, we collected 136 hESC and 69 hiPSC samples representing more than 100 cell lines for analysis. In order to establish expected variation in human tissues, we collected 80 high-quality and well-replicated samples representing 17 distinct tissue types from multiple individuals. Finally, we selected 50 additional samples from primary cell lines of diverse origin to control for any aberrations that may arise as a general, non-hPSC-specific, consequence of in vitro manipulation. With these samples, we performed genome-wide DNA methylation and mRNA expression profiling using the Illumina Infinium 27K and 450K DNA Methylation BeadChips as well as the Illumina HT12v3 Gene Expression BeadArray.
Experiment type
methylation profiling by array 
Contacts
Kristopher L. Nazor <kitnazor@scripps.edu>, Andrew L Laslett, Candace Lynch, Darryl D D'Lima, Eyitayo Fakunle, Francesca S Boscolo, Franz-Josef Müller, Gulsah Altun, Ha Tran, Hans S Keirstead, Hyun S Park, Ibon Garitaonandia, Ileana Slavin, Jeanne F Loring, Julie V Harness, Kristopher L Nazor, Louise C Laurent, Mana M Parast, Marina Martynova, Ruslan Semechkin, Sunray Lee, Tsaiwei Ole, Uli Schmidt, Vasiliy Galat, Yu-Chieh Wang
Citation
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives. Nazor KL, Altun G, Lynch C, Tran H, Harness JV, Slavin I, Garitaonandia I, Müller FJ, Wang YC, Boscolo FS, Fakunle E, Dumevska B, Lee S, Park HS, Olee T, D'Lima DD, Semechkin R, Parast MM, Galat V, Laslett AL, Schmidt U, Keirstead HS, Loring JF, Laurent LC. , PMID:22560082
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-30653.idf.txt
Sample and data relationshipE-GEOD-30653.sdrf.txt
Processed data (1)E-GEOD-30653.processed.1.zip
Additional data (1)E-GEOD-30653.additional.1.zip
Array designA-GEOD-8490.adf.txt
Links