Filters
Technology
Platform
GSE31831
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Targeting the estrogen signaling pathway has proved to be of great value in the treatment of human breast cancer. Tamoxifen, a selective estrogen receptor modulator (SERM), is the most widely used antiestrogen. However, only 40-50% of patients with estrogen receptor (ER) positive breast cancer benefit from tamoxifen treatment and 30-50% acquire resistance and the disease progresses. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug resistant cancer progenitors. We found that MCF7 tamoxifen-resistant (TAM-R) cells possess a significantly higher proportion of cancer progenitor cells than tamoxifen-sensitive MCF7 cells. Our results indicate that the chemokine receptor CXCR4 plays an important role in the maintenance of cancer progenitors in a tamoxifen-resistant cell line and downregulation of CXCR4 signaling by small molecule antagonists specifically inhibits growth of a stem-like cell population in tamoxifen-resistant tumors both in vitro and in vivo. Whole genome gene expression analysis revealed aryl hydrocarbon receptor (AhR) signaling as one of the top networks that is differentially regulated in MCF7(TAM-R) xenograft tumors treated with the CXCR4 antagonist AMD3100 as compared to MCF7 tumors. Further, small molecule antagonists of AhR signaling specifically inhibit the progenitor population in MCF7(TAM-R) cells suggesting that the aryl hydrocarbon receptor could be a putative target for the treatment of tamoxifen-resistant breast cancers. Introduction transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy.
Publication Title
CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human induced pluripotent stem (iPS) cells derived from somatic cells of patients hold great promise for modelling human diseases. Dermal fibroblasts are frequently used for reprogramming, but require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Here, we report the derivation of iPS cells from multiple human blood sources including peripheral blood mononuclear cells (PBMCs) harvested by routine venipuncture. Peripheral blood-derived human iPS lines are comparable to human embryonic stem (ES) cells with respect to morphology, expression of surface antigens, activation of endogenous pluripotency genes, DNA methylation and differentiation potential. Analysis of Immunoglobulin and T-cell receptor gene rearrangement revealed that some of the PBMC iPS cells were derived from T-cells, documenting derivation of iPS cells from terminally differentiated cell types. Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture. Reprogramming from blood cells thus represents a fast, safe and efficient way of generating patient-specific iPS cells.
Publication Title
Reprogramming of T cells from human peripheral blood.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs. immature neurons. We used immature (d0) and mature (d6) LUHMES cells (dopaminergic human neurons) to provide initial answers to these questions. Transcriptome profiling and characterization of energy metabolism suggested a switch from predominantly glycolytic energy generation to a more pronounced contribution of the tricarboxylic acid cycle (TCA) during neuronal maturation. Therefore, we used pulsed stable isotope-resolved metabolomics (pSIRM) to determine intracellular metabolite pool sizes (concentrations), and isotopically non-stationary 13C-metabolic flux analysis (INST 13C MFA) to calculate metabolic fluxes. We found that d0 cells mainly use glutamine to fuel the TCA. Furthermore, they rely on extracellular pyruvate to allow continuous growth. This metabolic situation does not allow for mitochondrial or glycolytic spare capacity, i.e. the ability to adapt energy generation to altered needs. Accordingly, neuronal precursor cells displayed a higher sensitivity to several mitochondrial toxicants than mature neurons differentiated from them. In summary, this study shows that precursor cells lose their glutamine dependency during differentiation while they gain flexibility of energy generation and thereby increase their resistance to low concentrations of mitochondrial toxicants.
Publication Title
Stage-specific metabolic features of differentiating neurons: Implications for toxicant sensitivity.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
In order to identify genes with different overall transcript levels or differential exon levels (alternative processing) between the groups Control and Tat-SF1KD, we studied 11 hybridizations on the HumanExon10ST array using mixed model analysis of variance. 526 genes with significant transcript level differences between the groups and 1397 genes with significant differential exon levels were found, including 99 genes with both transcript and exon level differences (p<0.01).
Publication Title
Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Expression data from Kc167 cells under normal conditions. Used to assess expression levels of genes with ORC bound at promoter.
Publication Title
Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2000
Description
In a fluorescence polarization screen for MYC-MAX interaction, we have identified a novel small molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. The Kd of KJ-Pyr-9 for MYC in vitro is 6.5 ± 1.0 nM as determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC-MAX complex formation in the cell as shown in a protein fragment complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in cell culture; it has no or only weak effects on the oncogenic activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation of MYC-overexpressing human and avian cells and specifically reduces the MYC-driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-overexpressing human cancer cells. Overall design: 4 treatment groups analyzed in triplicate: no treatment(control), 20uM KJ-Pyr-9, 0.1ug/mL doxycycline and KJ-Pyr-9 in combination with doxycycline
Publication Title
Inhibitor of MYC identified in a Kröhnke pyridine library.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Volatiles of certain rhizobacteria can cause growth inhibitory effects on plants/ Arabidopsis thaliana. How these effects are initiated and which mechanisms are enrolled is not yet understood. Obviously the plant can survive/live with the bacteria in the soil, which suggest the existance of a regulatory mechanism/network that provide the possibility for coexistance with the bacteria. To shed light on this regulatory mechanism/network we performed a microarray anlaysis of Arabidopsis thaliana co-cultivated with two different rhizobacteria strains.
Publication Title
Volatiles of two growth-inhibiting rhizobacteria commonly engage AtWRKY18 function.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Hordeum vulgare
- 12 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Caryopses of barley (Hordeum vulgare), like all other cereal seeds, are complex sink organs optimized for storage starch accumulation and embryo development. Their development from early stages after pollination to late stages of seed ripening has been studied in great detail. However, information on the caryopses diurnal adaptation to changes in light, temperature and alterations in phloem-supplied carbon and nitrogen remained unknown.
Publication Title
Significance of light, sugar, and amino acid supply for diurnal gene regulation in developing barley caryopses.
Sample Metadata Fields
Age, Specimen part
View Samples- Hordeum vulgare
- 12 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
High temperature stress, like any abiotic stress, impairs the physiology and development of plants, including the stages of seed setting and ripening.
Publication Title
Transcriptome analysis of high-temperature stress in developing barley caryopses: early stress responses and effects on storage compound biosynthesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Sample Metadata Fields
Cell line, Treatment
View Samples