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Homo sapiens
23 Downloadable Samples
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
DNA methylation changes in neuroblastoma, a clinically-heterogeneous pediatric tumor, have been described essentially in promoter regions. We analyzed the DNA methylome of neuroblastoma using high-density microarrays and observed differential methylation not only in promoters but also in intragenic and intergenic regions at both CpG and non-CpG sites. These epigenetic changes showed a non-random distribution relative functional chromatin domains, and targeted development and cancer-related genes, relevant for neuroblastoma pathogenesis. CCND1, a gene overexpressed in neuroblastoma, showed hypomethylation of gene-body and upstream regulatory regions. Furthermore, tumors with diverse clinical-risk showed clear differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation was present in clinically-favorable tumors and affected genes such as ALK, where non-CpG methylation correlated with low gene expression. Finally, we identified CpG and non-CpG methylation signatures which correlated with patients age at time-points relevant for neuroblastoma clinical behavior, and targeted genes related to neural development and neural crest regulatory network
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 75 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We set out to investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia (FRDA) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients. In the neuronal cell model, HDACi 109/RG2833 increases FXN mRNA levels and frataxin protein, with concomitant changes in the epigenetic state of the gene. Chromatin signatures indicate that histone H3 lysine 9 is a key residue for gene silencing through methylation and reactivation through acetylation, mediated by the HDACi. Drug treatment in FRDA patients demonstrated increased FXN mRNA and H3 lysine 9 acetylation in peripheral blood mononuclear cells. No safety issues were encountered.
Publication Title
Epigenetic therapy for Friedreich ataxia.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 64 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Duplication of the genome in mammalian cells occurs in a defined temporal order referred as its replication-timing program (RT). RT is regulated in units of 400-800 Kb referred as replication domains (RDs) and changes dynamically during development. Changes in RT are generally coordinated with transcriptional competence and changes in sub-nuclear position. We generated genome-wide RT profiles for 29 distinct human cell types including embryonic stem cell (hESC)-derived, primary cells and established cell lines representing intermediate stages of endoderm, mesoderm, ectoderm and neural crest (NC) development. We identified clusters of RDs that replicate at unique times in each stage (RT signatures). Surprisingly, transcriptome data revealed that, despite an overall correlation between early replication and transcriptional activity, most genes that switched RT during differentiation can be expressed when late replicating. Intriguingly, this class of genes was nonetheless induced to high expression levels prior to a late to early RT switch and down-regulated after the switch back to late replication. These results clarify the complex relationship between transcription and RT and identify classes of genes that behave as potential drivers of the RT switch vs. those that may depend upon an RT switch for transcriptional induction.
Publication Title
Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them good sources of cells for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a systematic study over more than 100continuous passages to identify characteristics of culture conditions (including passage method, substrate, and media type) that influence the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. The predominant effects we observed were increased genetic instability with enzymatic passage, higher cell proliferation with feeder-free substrate, and variations among cultures in global gene expression and DNA methylation with time in culture. We observed recurrent duplications in two genomic regions that have been noted in earlier studies to be hotspots for duplication in hPSCs, as well as a previously unreported recurrent deletion of the tumor suppressor gene TP53 in all but one of the long-term culture conditions; the exception was the condition using mechanical passaging on feeder layers. The deletion of TP53 is associated with decreased mRNA expression of TP53, as well as alterations in the expression of several other genes in the TP53 pathway, which taken together indicate a decrease in the function of the TP53 pathway. Our results highlight the need for careful assessment of effects of culture conditions on cells intended for clinical therapies.
Publication Title
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
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.
Publication Title
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples
GSE2394- Mus musculus
- 2 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
NMJ Junction various time points normal C57BL10 LCM mRNA
Publication Title
Intracellular expression profiling by laser capture microdissection: three novel components of the neuromuscular junction.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
NextSeq 500
Description
We investigated transcriptional responses of different lung macrophage lineages during M.tuberculosis infection by RNAseq. Our data revealed that different lineages of macrophages respond differentially to M.Tuberculosis infection. Overall design: Alveolar macrophage (AM) and interstitial macrophages (IM) with or without Mtb were FACS-sorted from Mtb infected mice for RNAseq.
Publication Title
Growth of <i>Mycobacterium tuberculosis</i> in vivo segregates with host macrophage metabolism and ontogeny.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples