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Homo sapiens
4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
To improve our understanding of the relationships between methylation and expression we profiled mRNA expression and single-base resolution methylation levels for two breast cancer cell lines, MCF7 and T47D. Expression was profiled using RNA-seq. Methylation was assayed using Methyl-MAPS, which uses methylation-sensitive and -dependent restriction enzyme digests followed by high-throughput sequencing to identify methylation levels at individual CpGs (Edwards et al. 2010, Genome Research). Overall design: RNA-Seq was used to generate mRNA expression profiles of MCF7 and T47D cells under standard growth conditions.
Publication Title
Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Approximately 75% of breast cancers express estrogen receptor a (ERa) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit estrogen receptor signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the up-regulation of alternative growth signals. The mechanisms that drive this resistance - especially epigenetic events that alter gene expression - are however not well understood. Here we performed a genome-wide DNA methylation and expression analysis of cell line models to find epigenetically regulated genes involved in acquired aromatase inhibitor resistance. We discovered that prostaglandin E2 receptor 4 (PTGER4) is up-regulated after demethylation and promotes phosphorylation and activation of ERa. Knockdown and inhibitor studies demonstrate that PTGER4 promotes AI resistance via ligand independent activation of the ERa-cofactor CARM1. We believe that we have discovered a novel epigenetic mechanism for altering cell signaling and acquiring endocrine therapy resistance. Our findings indicate that PTGER4 is a potential drug target in AI resistant cancers. Additionally, the epigenetic component of PTGER4 regulation suggests that further study of PTGER4 may yield valuable insights into how DNA methylation-targeted diagnoses and/or treatments can improve AI resistant breast cancer treatment. Overall design: RNA-Seq was used to generate mRNA expression profiles of MCF7-LTED (long-term estrogen deprived) cells grown in charcoal stripped serum. Two replicates were performed.
Publication Title
Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Arabidopsis RWP-RK protein RKD4 is expressed specifically in early embryogenesis and triggers embryonic cell division sequences. We used Affymetrix ATH1 microarrays to analyze the pattern of gene expression changes in response to induced ectopic expression of RKD4 in post-embryonic organs.
Publication Title
The Arabidopsis RWP-RK protein RKD4 triggers gene expression and pattern formation in early embryogenesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
The agonistic anti-human CD3 antibody , OKT-3, has been used to control acute transplant rejection. The in vivo administration of OKT-3 was previously shown to induce the partial depletion of T cells and anergy in the remaining CD4+ T cells. However, this therapy is also associated with the systemic release of several cytokines, which leads to a series of adverse side effects. We established a novel anti-human CD3 Ab, 20-2b2 (#1 abs), which recognized a close, but different determinant on the CD3 molecule from that recognized by OKT3. 20-2b2 was non-mitogenic for human CD4+ T cells, could inhibit the activation of T cells in vitro, and induced T cell anergy in in vivo experiments using humanized mice. Cytokine release in humanized mice induced by the administration of 20-2b2 was significantly less than that induced by OKT-3. Our results indicated that the CD3 molecule is still an attractive, effective, and useful target for the modulation of T cell responses. The establishment of other Abs that recognize CD3, even though the determinant recognized by those Abs may be close to or different from that recognized by OKT-3, may represent a novel approach for the development of safer Ab therapies using anti-CD3 Abs, in addition to the modification of OKT-3 in terms of the induction of cytokine production.
Publication Title
Modulation of the human T cell response by a novel non-mitogenic anti-CD3 antibody.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells.
Publication Title
Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ammonia is a toxic by-product of metabolism that causes cellular stress. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism that facilitate survival against toxicity have yet to be identified. We demonstrated that hypoxia-inducible factor-1 (HIF-1) is stabilised and activated by ammonia stress. HIF-1 activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation and glutamine-dependent metabolism under ammonia stress in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1 counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1 in biphasic ammonia stress management in cancer stem-like cells. GS facilitates proliferation and HIF-1 contributes to metabolic remodelling in cellular energy usage resulting in attenuated proliferation but conversely promoting cell survival.
Publication Title
Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To obtain insight into the genetic basis of the increase of functional activity of memory B cells over time, we compared the gene expression profiles of day 7 and day 40 NP-specific/IgG1 memory B cells, GC B cells and plasma cells in immunized WT mice and nave B cells, before and after activation in vitro.
Publication Title
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bcl6 germline deletion causes a prominent inflammatory disease, owing to over-expression of Th2 cytokines, and affects the properties of B cells prior to immunization. Therefore we established the B cell-specific Bcl6 deletion mice and analyze the gene expression of naive B cells under physiological conditions.
Publication Title
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory.
Sample Metadata Fields
Sex, Age
View Samples
GSE90034- Mus musculus
- 2 Downloadable Samples
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Multicellular organisms consist of multiple cell types, whose identities are maintained appropriately at locations where they are reside. The identity of each cell type is primarily maintained by cell-type-specific gene expression programs, but mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease -actin monomer resulted in nuclear accumulation of Mkl1 and the activation of Srf, which downregulated cell-type-specific genes and altered epigenetics in enhancers and chromatin organization. Mice overexpressing Srf exhibited various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.
Publication Title
Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.
Sample Metadata Fields
Specimen part
View Samples