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GSE10695
Bos taurus
36 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.
Publication Title
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 10 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Hyperimmune activation is one of the strong predictors of disease progression during pathogenic immunodeficiency virus infections and is mediated in part by sustained type I interferon (IFN) signaling. Combination antiretroviral therapy suppresses hyperimmune activation only partially in HIV-infected individuals. Here, we show that blockade of Programmed Death-1 (PD-1) during chonic SIV infection significantly reduces the expression of transcripts associated with type I IFN signaling in the blood and colorectal tissue of rhesus macaques (RM). The effect of PD-1 blockade on type I IFN signaling was durable and persisted under high viremia, a condition that is seen in nonprogressive SIV infection in their natural hosts. The reduced type I IFN signaling was associated with enhanced expression of some of the junction-associated genes in the colorectal tissue and a profound decrease in LPS levels in plasma suggesting a possible repair of gut associated junctions and decreased microbial translocation. The reduced type I IFN signaling was also associated with enhanced immunity against gut resident pathogenic bacteria, control of gut associated opportunistic infections and survival of SIV-infected RMs. These results reveal novel mechanisms by which PD-1 blockade enhances survival of SIV-infected RMs and have implications for development of novel therapeutic approaches to control HIV/AIDS.
Publication Title
PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activation of the Ras/Erk pathway upregulates expression of the Kruppel-like Factor 5 (KLF5) transcription factor, and KLF5 is a downstream mediator of Ras oncogenic signaling. Specifically, in bladder and colon cancer cell lines KLF5 upregulates the Ras-pathway target gene cyclin D1, and facilitates entry into the S phase of the cell cycle. Ras mutations are common in lung cancer, but a role for KLF5 in lung tumorigenesis has not been defined. To this end, we manipulated KLF5 expression in four Ras-mutant human lung adenocarcinoma cell lines to find that KLF5 significantly modulates anchorage-independent growth, a mutant Ras phenotype. However, in a mouse model of human lung adenocarcinoma, K-RasG12D does not critically require Klf5 to mediate oncogenesis or induce cyclin D1 expression.
Publication Title
Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 94 Downloadable Samples
Illumina HiSeq 2500
Description
Delineating key HSC regulators is of significant interest for informing the treatment of hematologic malignancy. While HSC activity is enhanced by overexpression of SKI, the transforming growth factor-beta (TGFß) signaling antagonist corepressor, its requirement in HSC is unknown. Here we reveal a profound defect in Ski-/- HSC fitness but not specification. Transcriptionally, Ski-/- HSC exhibited striking upregulation of TGFb superfamily signaling and splicing alterations. As these are both common aspects of myelodysplastic-syndrome (MDS) pathobiology with prognostic value, we investigated the role of SKI in MDS. A SKI-correlated gene signature defines a subset of low-risk MDS patients with active TGFß signaling and deregulated RNA splicing (e.g. CSF3R). The apparent paradox of Ski-/- HSC sharing molecular aspects of MDS with elevated SKI-mRNA is resolved by miR-21 targeting of SKI in MDS. We conclude that miR-21-mediated loss of SKI contributes to early stage MDS pathogenesis by activating TGFß signaling and alternative splicing while hindering HSC fitness. Overall design: Single cell RNA seq of transplanted fetal liver-derived hematopoietic stem cells
Publication Title
<i>SKI</i> controls MDS-associated chronic TGF-β signaling, aberrant splicing, and stem cell fitness.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Macaca mulatta
- 12 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
CD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is not clear how SIV infection is controlled in germinal center during chronic SIV infection and limited information exists on the characteristics of CXCR5+ CD8 T cells during chronic SIV/HIV infection. In this study, we used functional genomics to investigate characteristic features and potential mechanisms of CXCR5+ and CXCR5- SIV specific CD8 T cells for the control of pathogenic SIV infection. Six chronically SIV infected RMs, three SIVE660 infected and three SIV mac251 infected that are positive for Mamu A01 allele were selected and SIV-specific CXCR5+ and CXCR5- CD8 T cells were sorted based on CXCR5 expression. RNA from sorted cells were extracted and microarray were performed and analysed. Principal component analysis demonstrated that overall gene expression difference between CXCR5+ and CXCR5- SIV-specific CD8 T cells. Interestingly, the CXCR5+ CD8 T cells revealed a distinct gene signature pattern when compared to CXCR5- CD8 T cells. Unlike the CXCR5- CD8 T cells, the CXCR5+ CD8 T cells expressed higher levels of genes associated with Tfh CD4 T cells such as the master transcription factor Bcl6, CD200, and CTLA4 as well as markers associated with Th2 CD4 T cells such as IL-4R (CD124), CCR4, STAT6, NFATC, and IL-10. Effector molecules typically observed in cytotoxic CD8 T cells such as granzyme A, B, and K were expressed at lower levels on CXCR5+ CD8 T cells compared to their CXCR5- counterparts. CXCR5+ CD8 T cells also expressed higher levels of molecules associated with co-stimulation/antigen presentation such as CD40, CD83, 41BBL and MAMU-DRA. The CXCR5+ CD8 also expressed higher levels of inhibitory receptors such as CD200 and SPRY2 but lower levels of other inhibitory receptors CD160 and CD244. The functional consequence of the expression of these molecules is yet to be determined. Additionally, CXCR5+ CD8 T cells expressed higher levels of the anti-apoptotic gene Bcl-2 and lower levels of the pro-apoptotic gene annexin, suggestive of their better survival potential during chronic SIV infection. Collectively, these results demonstrate that SIV specific CXCR5+ CD8 T cells possess a unique gene expression signature compared to SIV-specific CXCR5- CD8 T cells.
Publication Title
Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 321 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the hosts inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 95 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.82). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.94, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.
Publication Title
Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.
Sample Metadata Fields
Race
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Recent observations about how cells sense amino acids have argued for preeminent roles of mTOR and the stress kinase GCN2 in allowing cells to estimate their amino acid needs. Here we used models of programmed immune microenvironments where helper T cells have to sense how much amino acids are available to engage in antigen-fueled proliferation. Contrary to current models, T cells activate mTOR in the competency phase of the cell cycle regardless of amino acid amounts, GCN2 or surface TCR. Instead, we found T cells use an amino acid sensing system to target IL-2-induced STAT5 phosphorylation at the restriction point of cell cycle commitment. mTOR activity is subsequently reduced and specifically connected to SREBP activation. T cells can be pushed into cycle by increasing IL-2 even when no amino acids are available. Collectively, our studies reveal helper T cells use sequential and distinct pathways to measure local amino acid concentrations.
Publication Title
Proliferating Helper T Cells Require Rictor/mTORC2 Complex to Integrate Signals from Limiting Environmental Amino Acids.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Integrins facilitate intercellular movement and communication. Unlike the promiscuous activities of many integrins, 6 integrin is restricted to epithelia and partners exclusively with integrin V to modulate acute lung injury (ALI). Given that ALI is a complication of respiratory infection, we used mice lacking 6 integrin (6 KO) to probe the role of the epithelial layer in controlling the lung microenvironment during infection. We found 6 KO mice were protected from disease caused by influenza and Sendai virus infections. They were also protected from disease caused by Streptococcus pneumoniae infection alone and after prior influenza virus infection, the co-infection representing an often-lethal condition in humans. Resistance in the absence of epithelial 6 integrin was caused by intrinsic priming of the lung microenvironment by type I interferons through a mechanism involving transforming growth factor- regulation. Expression of 6 on epithelia suppresses the production of interferons, providing an advantage to the pathogen. Acute inhibition of 6 function may therefore provide a means to improve outcomes in lung microbial infections.
Publication Title
An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
A total of 332 genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in ten human pterygium samples.
Publication Title
Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in three human pterygium samples.
Publication Title
Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
Sample Metadata Fields
No sample metadata fields
View Samples