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Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of resting (or surveying) microglia to an activated (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity.
Publication Title
Microglia in ischemic brain injury.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
IlluminaHiSeq2000
Description
Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies. Overall design: Primary analysis: 8 KD coronary arteries versus 7 childhood control coronary arteries. Subanalysis 1: 4 untreated KD coronary arteries versus 7 childhood control coronary arteries and subanalysis 2: 4 treated KD coronary arteries versus 7 childhood control coronary arteries
Publication Title
The transcriptional profile of coronary arteritis in Kawasaki disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 56 Downloadable Samples
- NextSeq 500
Description
We report the genome-wide RNA sequencing of bone marrow derived macrophages after sequential TLR agonist stimulation. Overall design: Examination of sequential TLR agonist stimulation. Bone marrow derived macrophages (BMDMs) were prepared from male animals 6-12 weeks of age. Cells were isolated from femurs and tibias. The bone marrow cells were and grown in macrophage growth medium (RPMI 1640 supplemented with 10% FBS (Gibco), 1% penicillin-streptomycin (Gibco), 2 mM L-glutamine (Gibco), 1 mM sodium pyruvate (Gibco), 0.01 M HEPES (AmericanBio), and 30% L929-conditioned media as a source of CSF-1), and plated on petri dishes. Macrophage growth medium was supplemented on day 3. Cells were plated for use on day 6. For sequential stimuli, cells were first stimulated with, PBS, 100 ng/mL Poly I:C (InvivoGen), or 5 ng/mL LPS derived from Escherichia coli 055:B5 (Sigma-Aldrich). 24 hours after the initial stimulation, the media was removed and cells were washed twice with warmed macrophage growth media, and then the media was replaced with Poly I:C or LPS.
Publication Title
Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Previous studies indicate that the triterpene glycoside actein from the herb black cohosh inhibits growth of human breast cancer cells. This study seeks to identify genes altered in human breast cancer cells by treatment with actein, using gene expression analysis. We treated MDA-MB-453 human breast cancer cells with actein at 2 doses, 20 or 40 g/mL, for 6 or 24 h. We identified 5 genes that were activated after each of the treatments that are known to play a role in cellular responses to diverse stresses, including the DNA damage and unfolded protein responses. In addition, four genes that mediate the integrated stress response (ISR), including activating transcription factor 4, were induced under at least one of the 4 treatment conditions. We used hierarchical clustering to define clusters comprising patterns of gene expression. Two ISR genes, activating transcription factor 3 (ATF3) and DNA damage- inducible transcript 3, and lipid biosynthetic genes were activated after exposure to actein at 40 g/mL for 6 h, whereas the cell cycle genes cyclin E2 and cell division cycle 25A were repressed. Our results suggest that actein induces 2 phases of the ISR, the survival phase and the apoptotic phase, depending on the dose and duration of treatment. We confirmed the results of gene expression analysis with real-time RT-PCR for 18 selected genes and Western blot analysis for ATF3. Since actein activated transcription factors that enhance apoptosis, and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.
Publication Title
The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- NextSeq 500
Description
In this manuscript, we described male-biased mutations in chrX genes in cancer. In this RNA-seq experiment we tested the transcriptional consequences of shRNA knockdown of one of those genes, CNKSR2 Overall design: Murine NIH 3T3 cells were infected with and selected for expression of lentiviruses expressing shRNAs targeting Cnksr2 (2 independent shRNA sequences) or a control shRNA (targeting RFP, a gene not present in these cells). Each was performed in biological triplicate independent cultures for n=9 total samples
Publication Title
Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: To compare the transcriptomes of IL-21-expressing, IL-21 and IL-4-expressing, and IL-4 expressing follicular helper T (Tfh) cells and Th2 cells in the spleen at 8 days following helminth infection Methods: Cell sorting of the populations was done for CD4+B220-CD44hiCXCR5hiPD-1hi cells of the various types, followed by mRNA purification. Overall design: CD4+Splenic T cell mRNA profiles 8 days post-infection of IL-21/IL-4 dual reporter mice with Nippostrongylus brasiliensis were generated by mRNA sequencing using Illumina HiSeq 2000.
Publication Title
TFH cells progressively differentiate to regulate the germinal center response.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to being causally linked to the formation of multiple tumor types, tobacco use has been associated with decreased anticancer treatment efficacy and reduced survival time. A detailed understanding of the cellular mechanisms that are affected by tobacco smoke should facilitate the development of improved preventive and therapeutic strategies. We have investigated the effects of a tobacco smoke (TS) extract on the transcriptome of MSK-Leuk1 cells, a cellular model of oral leukoplakia. Using Affymetrix HGU133 Plus 2 arrays, 411 differentially expressed probesets were identified. The observed transcriptome changes were grouped according to functional information, and translated into molecular interaction network maps and signaling pathways. Pathways related to cellular proliferation, inflammation, apoptosis and tissue injury appeared to be perturbed. Analysis of networks connecting the affected genes identified specific molecular interactions, hubs and key transcription regulators affected by TS. Thus TS was found to induce several EGFR ligands forming an EGFR-centered molecular interaction network, as well as several AhR-dependent genes, including the xenobiotic metabolizing enzymes CYP1A1 and CYP1B1. Notably, the latter findings in vitro are consistent with our parallel finding that levels of CYP1A1 and CYP1B1 were increased in oral mucosa of smokers. Collectively, these results offer insights into the mechanisms underlying the procarcinogenic effects of TS and raise the possibility that inhibitors of EGFR or AhR signaling will prevent or delay the development of tobacco smoke-related tumors. Moreover, the inductive effects of TS on xenobiotic metabolizing enzymes may help explain reduced efficacy of chemotherapy, and suggest targets for chemopreventive agents in smokers.
Publication Title
Effects of tobacco smoke on gene expression and cellular pathways in a cellular model of oral leukoplakia.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE5846- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
NCI-60 cancer cell lines were profiled with their genome-wide gene expression patterns using Affymetrix HG-U133A chips.
Publication Title
A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery.
Sample Metadata Fields
No sample metadata fields
View Samples GSE5845- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
40 bladder cancer cell lines were profiled with their genome-wide gene expression patterns using Affymetrix HG-U133A chips.
Publication Title
A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
T follicular helper (Tfh) cells are a subset of CD4+ T helper (Th) cells that migrate into germinal centers and promote B cell maturation into memory B and plasma cells. Tfh cells are necessary for promotion of protective humoral immunity following pathogen challenge, but when aberrantly regulated, drive pathogenic antibody formation in autoimmunity and undergo neoplastic transformation in angioimmunoblastic T-cell lymphoma and other primary cutaneous T-cell lymphomas. Limited information is available on the expression and regulation of genes in human Tfh cells. Using a fluorescence activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector (Teff) cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by ChIP-seq, with parallel transcriptome analyses determined by RNA-seq. Tfh cell enhancers were enriched near genes highly expressed in lymphoid cells or involved in lymphoid cell function, with many mapping to sites previously associated with autoimmune disease in genome-wide association studies. A group of active enhancers unique to Tfh cells associated with differentially expressed genes was identified. Fragments from these regions directed expression in reporter gene assays. These data provide a significant resource for studies of T lymphocyte development and differentiation and normal and perturbed Tfh cell function. Overall design: Using a fluorescence activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector (Teff) cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by ChIP-seq, with parallel transcriptome analyses determined by RNA-seq.
Publication Title
Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes.
Sample Metadata Fields
No sample metadata fields
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