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GSE5462
Homo sapiens
113 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation.
Publication Title
Changes in breast cancer transcriptional profiles after treatment with the aromatase inhibitor, letrozole.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells. Overall design: B cells derived from control and CD19-Cre;Id3loxP/loxP mice were activated in vitro in the presence of LPS and IL-4 for 24 or 48 hours. RNA was isolated from naïve as well as activated control and CD19-Cre;Id3loxP/loxP mice and analyzed by RNA-seq, in duiplicate.
Publication Title
Id3 Orchestrates Germinal Center B Cell Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The E-protein transcription factors E2A and HEB play important roles at several stages of hematopoiesis. However, the exact mechanism for theire action and the main targets in the LY6D negative common lymphoid progentior (CLP) compartment remains unknown. By adressing this question, we will gain important infromation regarding the early events leading to B-cell specification.
Publication Title
The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cell differentiation is known to involve changes in RNA expression, but little is known about translational control during differentiation. We comprehensively profiled gene expression during differentiation of embryonic stem cells (ESCs) into embyroid bodies (EBs) by integrating conventional transcriptome analysis with global assessment of ribosome loading. Differentiation was accompanied by an anabolic switch, characterized by global increases in transcript abundance, polysome content, protein synthesis rates and protein content. Furthermore, 78% of expressed transcripts showed increased ribosome loading, thereby enhancing translational efficiency. Elevated protein synthesis was accompanied by enhanced phosphorylation of eIF-4E binding protein, suggesting regulation by the mTOR pathway.
Publication Title
A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
Id proteins have been shown to promote the differentiation of conventional aß and ?dT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like ?dNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking ?dNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and ?dNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional aß T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells. Overall design: The RNA-Seq experiment included WT DP, pTaKO DP, L-DKO DP and L-DKO pTaKO (abbreviated as LP) DP cells (where L-DKO refers to mice deficient in both Id2/Id3). Each replicate represents cells from a single mouse. One pTaKO DP (#1) sample was removed from analysis due to low quality of sequencing. All mice were B6/129 hybrids and littermates.
Publication Title
Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although gain of chromosome-5p is one of the most frequent DNA copy number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study we showed that the microRNA processor Drosha (located on chromosome-5p) demonstrates frequent copy-number gain and over-expression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/over-expression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA-interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in eighteen cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of fourteen that were differentially-expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha over-expressing samples/cell lines was the highest-ranked change (by adjusted p-value) in both analyses, an observation validated by Northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes.
Publication Title
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sample Metadata Fields
Sex, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Foxo1 and Ebf1 deficiency leads to a similar disruption of normal B-cell development at the level of the common lymphoid progenitor (CLP). Both mouse strains display the existance of LY6D+ CLPs but a marked/complete lack of proB cells.
Publication Title
Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell antigen receptor (TCR)-driven signaling initially decreased the abundance of Id3, which led to the activation of a follicular regulatory T (TFR) cell–specific transcription signature. However, sustained lower abundance of Id2 and Id3 interfered with proper development of TFR cells. Depletion of Id2 and Id3 expression in Treg cells resulted in compromised maintenance and localization of the Treg cell population. Thus, Id2 and Id3 enforce TFR cell checkpoints and control the maintenance and homing of Treg cells. Overall design: Treg mRNA profiles in lymph node from 3-week-old Id2fl/flId3fl/fl;Foxp3Cre/Cre (Id2 Id3 double-knockout) and control mice are generated by deep sequencing.
Publication Title
Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Comparison of mRNA expression profiles in W12 Series 1 cervical ectokeratinocytes at passage number 22 versus 19 (during which time the cells gain an invasive phenotype)
Publication Title
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 71 Downloadable Samples
- IlluminaHiSeq2500
Description
We discovered induction of circular RNA in human fetal tissues, including the heart. In this study, we were able to recapitulate this induction by in vitro directed differentiation of hESCs to cardiomyocytes, paving the way for future studies into circular RNA regulation. Overall design: We harvested hESCs at sequential stages of differentiation: undifferentiated (day 0), mesoderm (day 2), cardiac progenitor (day 5) and definitive cardiomyocyte (day 14). We performed RNA sequencing in biological triplicate, with 3-8 technical replicates each.
Publication Title
Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.
Sample Metadata Fields
No sample metadata fields
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