Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30654 | GEO | 2012/05/14
SECONDARY ACCESSION(S): PRJNA144601
REPOSITORIES: GEO
Similar Datasets
Project 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.
| S-EPMC3348513 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE30652: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina HT12v3 Gene Expression] GSE30653: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina Infinium 27K DNA Methylation] GSE31848: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina Infinium 450K DNA Methylation] Refer to individual Series
2012-05-13 | E-GEOD-30654 | biostudies-arrayexpress
Project 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.
2012-05-14 | GSE31848 | GEO
Project 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.
2012-05-14 | GSE30653 | GEO
Project 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.
2012-05-13 | E-GEOD-31848 | biostudies-arrayexpress
Project 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.
2012-05-13 | E-GEOD-30653 | biostudies-arrayexpress
Project 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.
2012-05-14 | GSE30652 | GEO
Project 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.
2012-05-13 | E-GEOD-30652 | biostudies-arrayexpress
Project description:DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.
| S-EPMC2896277 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-09-24 | GSE37067 | GEO