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GSE52244
Homo sapiens
15 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
T-cell clones were obtained by limiting dilution culture of PBMC of HTLV-1 carriers. Exon expression profiling was performed using Affymetrix exon array (Affymetrix Human Exon 1.0 ST Array) according to the manufacturer's instructions. Gene version of CEL files 01 to 12 are presented in GSE46518.
Publication Title
HTLV-1-infected CD4+ T-cells display alternative exon usages that culminate in adult T-cell leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative 3-terminal exons, which use intronic polyadenylation sites, are generally unconserved and lowly expressed, while the main gene products end in the last exon of genes. In this study, we discover a class of human genes, where the last exon appeared recently during evolution, and the major gene product uses an alternative 3-terminal exon corresponding to the ancestral last exon of the gene. This novel class of alternative 3-terminal exons are down-regulated on a large scale by doxorubicin, a cytostatic drug targeting topoisomerase II, and play a role in cell cycle regulation, including centromere-kinetochore assembly. The RNA-binding protein, HuR/ELAVL1 is a major regulator of this specific set of alternative 3-terminal exons. HuR binding to the alternative 3-terminal exon in the pre-messenger RNA promotes its splicing, and is reduced by topoisomerase inhibitors. These findings provide new insights into the evolution, function and molecular regulation of alternative 3-terminal exons.
Publication Title
A recently evolved class of alternative 3'-terminal exons involved in cell cycle regulation by topoisomerase inhibitors.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 144 Downloadable Samples
Illumina HiSeq 2000
Description
Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation. Overall design: Pituitary Colony forming cells mRNA of 13-day old wild type (Prop1 +/+), Prop1 mutants (Prop1df/df), wild type (Pit1+/+) and Pit1 mutants (Pit1 dw/dw) mice were generated by deep sequencing, in triplicates.
Publication Title
PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Thyroid hormones, thyroxine and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1,145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way we could identify genomic targets of T3 in astrocytes and neurons, and in neuron subtypes, such as layer-specific neurons, and neurons expressing specific markers such as prepronociceptin, cholecystokinin, or cortistatin. T3 up-regulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport, and down-regulates genes involved in nuclear events, such as cell division, M phase of cell cycle, and chromosome organization and segregation. Remarkably the transcriptomic changes induced by T3 sustain the transition from embryonic to adult patterns of gene expression. The results allowed us to define in molecular terms the elusive role of thyroid hormones on neocortical development. Overall design: Pregnant dams were euthanized on gestational day 17.5, and the fetuses were extracted and euthanized by decapitation. The cerebral cortices were dissected, disaggregated and finally the cells were suspended in culture medium. After 9 days incubation cells were incubated for 24 hours before adding T3 at a final concentration of 10 nM. The cells were harvested 24 hours later. Cells without T3 were incubated in parallel. Cerebral cortices from individual fetuses originated two replicas for the cell culture, one with T3 and another without T3. Number of samples: 6.
Publication Title
Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina Genome Analyzer II
Description
T cell development comprises a stepwise process of commitment from a multipotent precursor. To define molecular mechanisms controlling this progression, we probed five stages spanning the commitment process using deep sequencing RNA-seq and ChIP-seq methods to track genome-wide shifts in transcription, cohorts of active transcription factor genes, histone modifications at diverse classes of cis-regulatory elements, and binding patterns of GATA-3 and PU.1, transcription factors with complementary roles in T-cell development. The results locate potential promoter-distal cis-elements in play and reveal both activation sites and diverse mechanisms of repression that silence genes used in alternative lineages. Histone marking is dynamic and reversible, and while permissive marks anticipate, repressive marks often lag behind changes in transcription. In vivo binding of PU.1 and GATA-3 relative to epigenetic marking reveals distinctive, factor-specific rules for recruitment of these crucial transcription factors to different subsets of their potential sites, dependent on dose and developmental context. Overall design: Genome-wide expression profiles, global distributions of three different histone modifications, and global occupancies of two transcription factors were examined in five developmentally related immature T populations. High throughput sequencing generated on average 9-30 million of mappable reads (single-read) for each ChIP-seq sample, and 10-15 million (single-read) for RNA-seq. Independent biological replicates were analyzed for individual populations. Terminology: FLDN1_RNA-seq_sample1 and FLDN1_RNA-seq_sample2 are independent biological replicates for the same cell type.
Publication Title
Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins involved in gene expression regulation, although their in vivo targets and activities in biological processes like cell differentiation, that requires reprogramming of gene expression programs at multiple levels, are not well characterized. In this report, we uncovered a new mechanism by which DDX5 and DDX17 cooperate with hnRNP H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms. We next observed that downregulation of DDX5 and DDX17 protein expression during epithelial to mesenchymal transdifferentiation and during myogenesis contributes to switching splicing programs during these processes. Remarkably, this downregulation is mediated by the production of microRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins master orchestrators of differentiation, that dynamically orchestrate several layers of gene expression.
Publication Title
RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 96 Downloadable Samples
- NextSeq500
Description
We utilize gene expression and open chromatin footprinting data to build a gene regulatory network of key transcription factors that capture the cell and time-specific regulatory programs specified during human myeloid differentiation. Overall design: RNA-seq profiling of undifferentiated HL-60, differentiating macrophage, neutrophil, monocyte, and monocyte-derived macrophage cells.
Publication Title
Dynamic Gene Regulatory Networks of Human Myeloid Differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 29 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Background: Extended hepatectomies may result in post-hepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy.
Publication Title
Gene Expression in the Liver Remnant Is Significantly Affected by the Size of Partial Hepatectomy: An Experimental Rat Study.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 92 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel genes associated with lymph node metastasis in triple negative breast cancer.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis. It is characterised by the absence of hormone receptors for estrogen, progesterone, and human epidermal growth factor 2, and as a consequence there are no targeted endocrine treatments available. TNBC patients are more likely to develop metastases and disease relapse than patients with other breast cancer subtypes. The identification of biomarkers that can be used to predict which patient is likely to develop metastatic disease remains a priority since this is the major cause of cancer-related death in these women.
Publication Title
Novel genes associated with lymph node metastasis in triple negative breast cancer.
Sample Metadata Fields
Specimen part
View Samples