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GSE19169
Mus musculus
29 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 29 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to detail the role of JMJ in ES cell function.
Publication Title
Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
The Polymerase Associated Factor (PAFc) complex is an epigenetic regulating complex that has been shown to to be important for Acute Myeloid Leukemias harboring an MLL chromosomal translocations, such as MLL-AF9 leukemias. This study describes the transcriptomic profiling of AML cells following genetic deletion of the PAFc subunit Cdc73. Overall design: Cdc73floxed cells were transformed to an AML using MLL-AF9 oncogene transduction. The cells were also transduced with a 4OHT inducible CreER. The cells were then treated for 24 or 48 hours with 4OHT to induce genetic excision of Cdc73 and polyA mRNA was isolated for sequencing of the transcriptome. Biological duplicates are labelled _1 and _2.
Publication Title
The PAF complex regulation of Prmt5 facilitates the progression and maintenance of MLL fusion leukemia.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 71 Downloadable Samples
- Illumina HiSeq 4000
Description
In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the Eif2ak2-Eif2a axis is the key mediator of translation initiation block in late phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings implicate that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis. Overall design: Bulk 20 um thickness specimens from cross-sectional human kidney biopsies embedded in OCT underwent RNA sequencing. All subjects had ATN, AIN, or a mix of both conditions.
Publication Title
Bacterial sepsis triggers an antiviral response that causes translation shutdown.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
High serum concentrations of kidney-derived protein uromodulin (Tamm-Horsfall protein or THP) have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage. THP in the serum dropped after AKI, and was associated with an increase in systemic ROS. The increase in oxidant injury correlated with post-surgical mortality and need for dialysis. Mechanistically, THP inhibited the activation of the TRPM2 channel. Furthermore, inhibition of TRPM2 in vivo in a mouse model, mitigated the systemic increase in ROS during AKI and THP deficiency. Our results suggest that THP is a key regulator of systemic oxidative stress by suppressing TRPM2 activity and our findings might help to explain how circulating THP deficiency is linked with poor outcomes and increased mortality.
Publication Title
Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Mouse glioblastomas were induced by lentiviral vector expressing HrasG12V and shRNA against p53. Tumor tissues were isolated from mice reached clinical endpoints. RNA was isolated using the RNeasy kit according to manufacturer’s protocol with the addition of DNase (Qiagen). cDNA libraries were prepared using the TruSeq RNA Sample Prep kit (Illumina). RNA sequencing was performed using a HiSeq 2500 Sequencing System (Illumina). Overall design: 3 normal mouse brain samples compared to 5 glioblastoma samples by standard RNAseq method.
Publication Title
Targeting NF-κB in glioblastoma: A therapeutic approach.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. The purpose of this experiment was to characterize the transcriptomic changes associated with macrophage aging.
Publication Title
Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
The identification of Atg16L1 as a susceptibility gene has implicated antibacterial autophagy in the pathogenesis of Crohn''s disease, a major type of inflammatory bowel disease (IBD). However, the role of Atg16L1 during extracellular bacterial infections of the intestine has not been sufficiently examined and compared to the function of other IBD susceptibility genes such as Nod2. We now find that Atg16L1 mutant mice are extraordinarily resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. We further demonstrate that Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, and that Atg16L1/Nod2 double mutant mice lose this advantage. These results reveal an unappreciated immuno-suppressive function of an IBD gene, and raise the possibility that gene variants that affect the autophagy pathway were evolutionarily maintained to protect against certain life-threatening infections. Overall design: Twenty samples have been analyzed. All are colonic tissue from mice. Controls are uninfected WT mice, uninfected Atg16L1 mutant mice (Atg16L1HM) (n=3/genotype). Treatment conditions are tissue from WT and Atg16L1 mutant mice 6 days after C. rodentium infection (n=4/genotype) and 15 days after infection (n=3/genotype).
Publication Title
A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HiSeq 2500
Description
Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T cells in a background of chronic inflammation. Dendritic cells (DCs) are potent T-cell stimulators; yet despite DCs' extensive presence in skin, cutaneous T cells in CTCL do not respond with effective anti-tumor immunity. We evaluated primary T-cell and DC émigrés from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5). Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3; and CD8+ CTCL populations comprised more T cells expressing CTLA-4 and LAG-3. CTCL populations also contained more T cells expressing the inducible T-cell costimulator (ICOS), a marker of T-cell activation. DC émigrés from healthy or CTCL skin biopsies expressed PD-L1, indicating that maturation during migration resulted in PD-L1 expression irrespective of disease. Most T cells did not express PD-L1. Using skin samples from 49 additional CTCL patients for an unsupervised analysis of genome-wide mRNA expression profiles corroborated that advanced T3/T4 stage samples expressed higher levels of checkpoint inhibition genes compared with T1/T2 stage patients or healthy controls. Exhaustion of activated T cells is therefore a hallmark of both CD4+ and CD8+ T cells directly isolated from the lesional skin of patients with CTCL, with a continuum of increasing expression in more advanced stages of disease. These results justify identification of antigens driving T-cell exhaustion and the evaluation of immune checkpoint inhibition to reverse T-cell exhaustion earlier in the treatment of CTCL. Overall design: RNA-seq correlated with tumor stages
Publication Title
Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 221 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In Huntingtons disease (HD), expanded HTT CAG repeat length correlates strongly with age at motor onset, indicating that it determines the rate of the disease process leading to diagnostic clinical manifestations. Similarly, in normal individuals, HTT CAG repeat length is correlated with biochemical differences that reveal it as a functional polymorphism. Here, we tested the hypothesis that gene expression signatures can capture continuous, length-dependent effects of the HTT CAG repeat. Using gene expression datasets for 107 HD and control lymphoblastoid cell lines, we constructed mathematical models in an iterative manner, based upon CAG correlated gene expression patterns in randomly chosen training samples, and tested their predictive power in test samples. Predicted CAG repeat lengths were significantly correlated with experimentally determined CAG repeat lengths, whereas models based upon randomly permuted CAGs were not at all predictive. Predictions from different batches of mRNA for the same cell lines were significantly correlated, implying that CAG length-correlated gene expression is reproducible. Notably, HTT expression was not itself correlated with HTT CAG repeat length. Taken together, these findings confirm the concept of a gene expression signature representing the continuous effect of HTT CAG length and not primarily dependent on the level of huntingtin expression. Such global and unbiased approaches, applied to additional cell types and tissues, may facilitate the discovery of therapies for HD by providing a comprehensive view of molecular changes triggered by HTT CAG repeat length for use in screening for and testing compounds that reverse effects of the HTT CAG expansion.
Publication Title
Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy.
Sample Metadata Fields
Sex
View Samples