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GSE82051
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interactions between Chronic Lymphocytic Leukemia B-cells (CLL B-cells) and the microenvironment (ME) play a major function in the physiopathology of CLL. Extracellular vesicles (EVs) (composed of exosomes and microparticles) have been shown to play an important role in cell communication. EVs, purified by ultracentrifugation from bone marrow mesenchymal stromal cells (BM-MSC) culture, were added to CLL B-cells. Microarray study highlighted 805 differentially expressed genes between CLL-B-cells cultured with and without EVs. Of these, CCL3/4, EGR1/2/3, MYC (involved in BCR pathway) were increased while pro-apoptotic genes like HRK were decreased. We showed for the first time the potential of EVs alone to induce gene expression modifications in CLL B-cell, notably in BCR and apoptosis pathways. We concluded that a substantial part of communication between CLL B-cells and BM-ME is mediated through EV.
Publication Title
Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines.
Publication Title
Multifactorial approach to predicting resistance to anthracyclines.
Sample Metadata Fields
Disease stage
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Endocycle is an alternative cell cycle during which the DNA is replicated in the absence of cytokinesis, resulting in cellular endopolyploidy. The endocycle is frequenctly observed in plant species that grow under extreme conditions. Thus, endopolyploidy has been postulated to be a mechanism facilitating adaptive growth.
Publication Title
A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the Endocycle in Root Development and Stress Adaptation.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 5 Downloadable Samples
NextSeq 500
Description
Somatic polyploidy caused by endoreplication is observed in arthropods, molluscs, and vertebrates, but is especially prominent in higher plants where it has been postulated to be essential for cell growth and fate maintenance. However, a comprehensive understanding of the physiological significance of plant endopolyploidy has remained elusive. Here, we modeled and experimentally verified a high-resolution DNA endoploidy map of the developing Arabidopsis thaliana root, revealing a remarkable spatiotemporal control of DNA endoploidy levels across tissues and a strong dependence on stress signals. Cellular and transcriptomic analysis revealed that inhibition of endoreplication onset alters the nuclear-to-cellular volume ratio and change in expression of cell wall modifying genes, correlated with the appearance of cell structural changes. Our data indicate that endopolyploidy might serve to coordinate cell expansion with structural stability, and that spatiotemporal endoreplication pattern changes may buffer for stress conditions, which may explain the widespread occurrence of the endocycle in plant species growing in extreme or variable environments. Overall design: Two biological replicates of Col-0 were compared with three biological replicates of smr1
Publication Title
A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the Endocycle in Root Development and Stress Adaptation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The NF1 tumor suppressor encodes a RAS GTPase-Activating Protein (RasGAP). Accordingly, deregulated RAS signaling underlies the pathogenesis of NF1-mutant cancers. However, while various RAS effector pathways have been shown to function in these tumors, it is currently unclear which specific proteins within these broad signaling pathways represent optimal therapeutic targets. Here we identify mTORC1 as the key PI3K pathway component in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. We also report that combined mTORC1/MEK inhibition is required to promote tumor regression in animal models, but only when the inhibition of both pathways is sustained. Transcriptional profiling studies were also used to establish a predictive signature of effective mTORC1/MEK inhibition in vivo. Within this signature, we unexpectedly found that the glucose transporter gene, GLUT1, was potently suppressed but only when both pathways were effectively inhibited. Moreover, unlike VHL and LKB1 mutant cancers, reduction of 18F-FDG uptake measured by FDG-PET required the effective suppression of both mTORC1 and MEK. Together these studies identify optimal and sub-optimal therapeutic targets in NF1-mutant malignancies and define a non-invasive means of measuring combined mTORC1/MEK inhibition in vivo, which can be readily incorporated into clinical trials.
Publication Title
Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 96 Downloadable Samples
- Illumina HiSeq 1500
Description
We have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)
Publication Title
<i>Mycobacterium tuberculosis</i> Invasion of the Human Lung: First Contact.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 92 Downloadable Samples
- Illumina HiSeq 1500
Description
We have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)
Publication Title
<i>Mycobacterium tuberculosis</i> Invasion of the Human Lung: First Contact.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
mTOR and HDAC inhibitors induce cell death of malignant peripheral nerve sheath tumors (MPNSTs) in vitro, and in vivo
Publication Title
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues. Overall design: 6 samples in total: 3 control, 3 siRNA MCM7
Publication Title
Resting cells rely on the DNA helicase component MCM2 to build cilia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues. Overall design: 6 samples in total: 3 control, 3 siRNA MCM2
Publication Title
Resting cells rely on the DNA helicase component MCM2 to build cilia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples