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Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2000
Description
Hepatocellular carcinoma (HCC) accounts for the majority of malignant liver tumors and results in many deaths each year, emphasizing the need for new therapies. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Therefore, we performed RNA sequencing experiment to determine the transcriptome change in the HepG2 cells upon treatment of MI-503, a small molecule inhibitor of the menin-MLL1 interaction with optimized drug-like properties Overall design: HepG2 cells were plated in the 12-well plates at the initial concentration of 0.4x106 cells/ml and treated with 3 µM MI-503 or DMSO (0.25%) in triplicates. After 3 days of treatment viable cell number was adjusted to the original concentration in the DMSO treated samples and the same dilution factor was used to adjust cell number in the MI-503 treated cells. Media was changed and compound or DMSO was re-supplied at that time. Cells were harvested after 3 more days of incubation.
Publication Title
Pharmacologic Inhibition of the Menin-MLL Interaction Leads to Transcriptional Repression of <i>PEG10</i> and Blocks Hepatocellular Carcinoma.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T lymphocytes can be generated from T-cell-derived induced pluripotent stem cells (T-iPS). We used microarrays to better elucidate their phenotype and compare their gene expression profile to that of known lymhoid subsets from peripheral blood.
Publication Title
Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 60 Downloadable Samples
- NextSeq 500
Description
Pioneer transcription factors are able to recognise and bind their motif sequences in inaccessible or closed chromatin, and their ability to achieve this is required to establish new regulatory elements and transcriptional networks during development and cellular reprogramming. An essential feature of this pioneering activity is the transition from inaccessible chromatin to a nucleosome-depleted and accessible chromatin state typical of normal regulatory elements, and this is believed to facilitate further transcription factor binding events. However, the mechanisms by which many pioneer transcription factors achieve this remarkable feat remain elusive. Here we reveal that the pluripotency-associated pioneer factor OCT4 binds inaccessible chromatin to shape the chromatin accessibility, transcription factor co-binding and regulatory potential of thousands of distal regulatory elements in mouse embryonic stem cells, demonstrating that its pioneering activity is a feature of normal pluripotency, and not just reprogramming. The accessible chromatin formed at OCT4 binding sites relies on the chromatin remodelling factor BRG1, which is recruited to these sites by OCT4. The occupancy of BRG1 is then required to support OCT4/SOX2 co-binding and normal expression of the pluripotency-associated transcriptome, and this reliance on BRG1 reflects OCT4 binding dynamics during cellular reprograming and early mouse development. Together these observations reveal a distinct requirement for the chromatin remodelling factor BRG1 in shaping the pioneering activity of OCT4 and regulating the pluripotency network in embryonic stem cells. Overall design: ZHBTC4 and Brg1fl/fl mouse embryonic stem cells were used to ablate OCT4 and BRG1 expression respectively, followed by ATAC-seq, ChIP-seq or RNA-seq to examine their contribution towards chromatin accessibility, transcription factor occupancy, and gene expression.
Publication Title
The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recently, the bone marrow (BM) has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4+ and CD8+ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of nave and an increase in effector-memory T cells. In contrast to the peripheral blood (PB), a highly activated CD8+CD28 T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation and differentiation of CD8+ T cell in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8+CD28 T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4+ and CD8+ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8+CD28 T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.
Publication Title
The impact of aging on memory T cell phenotype and function in the human bone marrow.
Sample Metadata Fields
Sex, Age
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Impaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as causing increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an “epiallele,” being inherited for multiple generations before fully resetting. Derepression was not restricted to the transgene but was caused by a global reduction in heterochromatin-associated histone modifications due to the impaired retention of modified histones on DNA during replication in the early embryo. Impaired DNA replication during development can therefore globally derepress chromatin, creating new intergenerationally inherited epigenetic expression states. Overall design: 3 replicates of div-1 mutant worms and N2 wild type worms
Publication Title
Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Embryonic mouse brain development involves a sequential differentiation of multipotent progenitor cells into neurons and glia. Using microarrays and large 2-D electrophoresis, we investigated the transcriptome and proteome of mouse brains at embryonic days 9.5, 11.5 and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuronal differentiation. As expected, we detected numerous expression changes between the time points investigated but interestingly, the rate of alteration was about 10% to 13% of all proteins and mRNAs during every two days of development. Furthermore, up- and downregulation was balanced. This was confirmed for two additional stages of development, embryonic day 16 and 18. We hypothesize that during embryonic development, the rate of protein expression alteration is rather constant due to a limitation of cellular resources such as energy, space and free water. The similar complexity found at the transcriptome and proteome level at all stages suggests, that changes in relative concentration of gene products rather than an increased number of gene products dominate throughout cellular differentiation. We found that metabolism and cell cycle related gene products were downregulated in expression when precursor cells switched from proliferation to neuronal differentiation (day 9.5 to 11.5), whereas neuron specific gene products were upregulated. A detailed analysis revealed their implication in differentiation related processes such as rearrangement of the actin cytoskeleton as well as Notch and Wnt signaling pathways.
Publication Title
Transcriptome and proteome analysis of early embryonic mouse brain development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The roles of histone demethylase RBP2 in gene expression were assessed using gene expression profiling experiments with wild type and RBP2-/- primary MEFs. Several cytokine genes including SDF1 and Kit ligand were upregulated upon inactivation of RBP2.
Publication Title
The retinoblastoma binding protein RBP2 is an H3K4 demethylase.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Establishment of a transcriptomic profile of human cells treated with kaemferol, daidzein, kaemferol/genistein, or daidzein/genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein influence expression of some genes, among which are those coding for enzymes required for the synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein at the molecular level in terms of modulation of gene expression.
Publication Title
Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 51 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the different inducible cell lines
Publication Title
Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.
Sample Metadata Fields
Specimen part
View Samples
GSE21746- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A tissue-specific landscape of sense/antisense transcription in the mouse intestine.
Sample Metadata Fields
Specimen part
View Samples