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GSE66354
Homo sapiens
146 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inflammatory response has been identified as a molecular signature of high-risk Group A ependymoma (EPN). To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN group A inflammation.
Publication Title
Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The NF-B pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-B response is regulated by the activation state of the IB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-B is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-B activation and the potential importance of NF-B in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-B activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo.
Publication Title
The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptional profiling of Murine BaF3 cells infected with MPLW515L grown under either normal conditions (Naive) or in 0.8 uM INCB18424 for 4-6 weeks (Persistent). Naive and Persistent cells were then treated with either DMSO (Control) or 0.8 uM INCB18424 for 4 hours. Goal was to determine transcriptional changes conditioned upon sensitivity/resistance of BaF3 MPLW515L mutants to JAK1/2 specific inhibitor.
Publication Title
Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy.
Sample Metadata Fields
Disease, Cell line
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The TEL-JAK2 fusion oncogene and the ICN1 activated allele of NOTCH1 are the result of specific chromosomal translocations in T cell acute lymphoblastic leukemia (T-ALL). Mouse models of these diseases (TEL-JAK2 transgenic mice; Carron C. et al. Blood (2000); a bone marrow transplantation model for ICN1-induced T-ALL) were used to compare the transcriptional program specific to each oncoprotein in mouse models of these leukemias. Tumor load was >50% leukemic cells in all selected organs.
Publication Title
Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 287 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The goal of this study is to characterize the human immune responses to the live attenuated Herpes zoster vaccine Zostavax, to understand the molecular and cellular mechanisms that lead to antibody production and T cell induction, and to understand the difference between young and elderly healthy adults. The overall data collection included antigen specific assays, flow cytometric profiling of innate and adaptive cell populations, measurement of serum cytokines, and transcriptomic and metabolomics signatures. Zostavax induced robust antigen-specific antibody responses, and significant T cell responses. A number of gene pathways were upregulated after vaccination. Using our previously developed blood transcription modules, we also identified transcriptomic correlates to antibody response. Furthermore, this study revealed strong association between PBMC transcriptomics and plasma metabolomics. Integrative analysis of orthogonal datasets from metabolomics, transcriptomic and immune profiling facilitated a temporal reconstruction of Zostavax induced biological networks culminating in antibody responses , and the delineation of novel molecular correlates of vaccine immunity.
Publication Title
Metabolic Phenotypes of Response to Vaccination in Humans.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Subject
View Samples- Homo sapiens
- 55 Downloadable Samples
NextSeq 500
Description
The Myc/Max heterodimer has crucial roles in normal cellular processes such as cell proliferation, metabolism, apoptosis, and differentiation, but its activity is often deregulated in a majority of human cancers. In an effort to explore alternative modes of Myc perturbation, we identified KI-MS2-008 as a small molecule that binds Max and modulates Myc-driven transcription, and in some cellular contexts, KI-MS2-008 treatment leads to a decrease in c-Myc protein levels. As the Myc/Max heterodimer controls many cellular processes, we expected that treatment with this small molecule would cause changes in the transcriptome. We found that treatment with 10 µM KI-MS2-008 resulted in global alterations in the transcriptome, mimicking direct Myc inactivation with doxycycline in P493-6, a B cell line with a Tet-Off system for c-Myc expression. We also discovered enrichment of various Myc target gene sets in the genes downregulated in response to KI-MS2-008 treatment in P493-6 cells. This trend was also observed in ST486 cells, but not in P3HR1 cells, which were chosen as non-engineered B cell lines that were sensitive and insensitive, respectively, toward KI-MS2-008 in cell viability assays. Overall design: RNA-seq characterizing three B cell lines: P493-6 (an engineered, KI-MS2-008 sensitive cell line), ST486 (a non-engineered, KI-MS2-008 sensitive cell line), and P3HR1 (a non-engineered, KI-MS2-008 insensitive cell line). P493-6 cells were treated with 0.1 µg/mL doxycycline, 1 µM KI-MS2-008, 10 µM KI-MS2-008, or 0.4% DMSO for 45 minutes or 8 hours. ST486 cells were treated with 1 µM KI-MS2-008, 10 µM KI-MS2-008 or 0.4% DMSO for 45 minutes or 8 hours. P3HR1 cells were treated with 10 µM KI-MS2-008 or 0.4% DMSO for 8 hours. 4 replicates were performed for each condition.
Publication Title
Stabilization of the Max Homodimer with a Small Molecule Attenuates Myc-Driven Transcription.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Global expression profiling of airway epithelial cells infected with Pseudomonas aeruginosa and the rsmA mutant.
Publication Title
Pseudomonas aeruginosa infection of airway epithelial cells modulates expression of Kruppel-like factors 2 and 6 via RsmA-mediated regulation of type III exoenzymes S and Y.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
There is much controversy about the role of T-regulatory cells (Treg) in human colon cancer. High densities of tumor-infiltrating Treg can correlate with better or worse clinical outcomes depending on the sutdy. Treg have potent anti-inflammatory functions that have been shown to control cancer progression. However, Treg isolated from patient with colon cancer or in mouse models of polyposis do not have the ability to suppress inflammation and instead promote cancer. Gene expression was preformed to determine differences between Treg isolated from healthy mice and Treg isolated from polyp-ridden mice.
Publication Title
Expression of RORγt marks a pathogenic regulatory T cell subset in human colon cancer.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand–receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process. Overall design: Total of 16 mice brains with raw data for 50,212 single cells and processed data for 37,089 single cells
Publication Title
Single-cell transcriptomic profiling of the aging mouse brain.
Sample Metadata Fields
Specimen part, Subject
View Samples