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SRP144689
Mus musculus
12 Downloadable Samples
NextSeq 500
Description
Despite the prevalence and recognition of its detrimental impact, clinical complications of sepsis remain a major challenge. Here, we investigated the effects of myeloid ferritin heavy chain (FtH) in regulating the pathogenic sequelae of sepsis. We demonstrate that deletion of myeloid FtH leads to tolerance towards sepsis as evidenced by reduced serum cytokine levels, multi-organ dysfunction and subsequent mortality. We identified that such tolerance is predominantly mediated by the compensatory increase in circulating ferritin (ferritin light chain; FtL) in the absence of myeloid FtH. Our in vitro and in vivo studies indicate that prior exposure to ferritin provides significant tolerance to the septic process by restraining an otherwise dysregulated response to infection. These findings are mediated by an inhibitory action of ferritin on NF-?B activation and its downstream effects. Taken together, our findings suggest an essential immunomodulatory function for circulating ferritin and enhances our understanding of this acute phase reactant. Overall design: Total RNA were isolated from blood leukocytes of wild type FtH mice and Myeloid deficient FtH mice following sham and CLP surgery. Three biological replicates were considered for each genotype and surgery type.
Publication Title
Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 77 Downloadable Samples
- Illumina HiSeq 2500
Description
We use time series RNA-seq to conduct a genome-wide survey of the temporal transcriptome response of human embryonic stem (ES) cell-derived neural progenitor cells (NPCs) exposed to lead. Overall design: NPCs were derived from human embryonic stem cells (hESCs) with a modified protocol from a previously reported protocol (Chambers et al. 2009) (Methods). We used lead acetate to treat NPCs at two different concentrations, 3 µM and 30 µM.
Publication Title
RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations.
Sample Metadata Fields
Specimen part, Subject
View Samples- Bos taurus
- 18 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Selenium (Se) is an essential nutrient for beef cattle health and commercial production. The molecular mechanisms responsible for the physiological responses of the animal to dietary Se supplementation, however, have not been evaluated. Furthermore, the potential effect of two chemical forms (organic vs. inorganic) of Se on gene expression by Se-sufficient cattle has not been evaluated.
Publication Title
Dietary supplementation of selenium in inorganic and organic forms differentially and commonly alters blood and liver selenium concentrations and liver gene expression profiles of growing beef heifers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chronic loss of Lasp1 alters the expression of other genes associated with cell motility/attachment, and/or other cellular functions. Results provide new information showing that loss of Lasp1 leads to up- and down-regulation of genes involved in cell motility/attachment/growth.
Publication Title
Lasp1 gene disruption is linked to enhanced cell migration and tumor formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 61 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
NOD mice were injected once a week with LTBR-Ig to block the LTBR-pathway, or with control monoclonal antibody MOPC from age 8 to 16 weeks old. Extraorbital lacrimal glands or submaxillary glands were dissected and total mRNA prepared. Each sample was either the combined lacrimals (2) from each mouse or individual salivary glands. There were 4 mice in each treatment group. Total mRNA was isolated and the quality was assessed using the Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). Reverse transcription to prepare cDNA was performed using Invitrogen M-MLV system. The purpose was to determine changes in gene expression in glands due to blockade of the LTBR-pathway.
Publication Title
Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Respiratory innate immunity requires alveolar macrophages, which are specifically targeted by the S. aureus toxin alpha toxin. These data compare the response of alveolar macrophages to S. aureus with or without alpha toxin neutralization.
Publication Title
S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 303 Downloadable Samples
- IlluminaHiSeq2500
Description
Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials, and offer a cost effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically-defined poly(ethylene glycol) (PEG) hydrogels and cultured in serum-free media to model cellular interactions of the developing brain. The precursors self-assembled into 3-dimensional (3D) neural constructs with cortically organized neuronal and glial cells, interconnected vascular networks, and ramified microglia. Replicate constructs were highly reproducible by RNA sequencing (Spearman's correlation coefficients, ? = 0.97) and robustly expressed neurogenesis, vasculature development, and microglia genes. Finally, linear support vector machines were used to construct a predictive model from RNA sequencing data for 240 neural constructs treated with 60 toxic and non-toxic chemicals, which then correctly classified 9/10 blinded compounds. Overall design: Note that all cell types were derived from the H1 human embryonic stem cell line. 11 samples for initial quality control (triplicate day 13 neural progenitor cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells and migroglia/macrophage precursor cells), quadruplicate samples of H1 ES cells as a control for comparing to untreated toxicity study samples, and 288 samples associated with toxicity screening (all samples formed using neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors).
Publication Title
Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.
Publication Title
Adenoviral Vector Vaccination Induces a Conserved Program of CD8(+) T Cell Memory Differentiation in Mouse and Man.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
- Illumina HiSeq 3000
Description
Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R) but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited and the few remaining tumors were of low grade dysplasia. RNA-Seq analysis demonstrated downregulation of STAT3 and Wnt pathway components. Since EGF-R on myeloid cells, but not on intestinal epithelial cells is required for intestinal cancer and IL-6 is induced via EGF-R stimulation, we analyzed the role of IL-6 signaling. Tumor formation was equally inhibited in IL-6 -/- and sgp130Fc transgenic mice, in which only trans-signaling via soluble IL-6R is abrogated. ADAM17 is needed for EGF-R-mediated induction of IL-6 synthesis, which via IL-6 trans-signaling induces ß-catenin dependent tumorigenesis. Our data reveal the possibility of a novel strategy for treatment of colorectal cancer, which could circumvent intrinsic and acquired resistance to EGF-R blockade. Overall design: RNA sequencing of tumor tissue and surrounding unaffected tissue of Apc Min/+ and Apc Min/+ ::ADAM17 ex/ex
Publication Title
ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pharmacological and gene ablation studies have demonstrated a crucial role of the cardiac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. In addition, hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative NP deficiency. Hence the study of the function of the endocrine heart is highly relevant.
Publication Title
Transcriptional analysis of the mammalian heart with special reference to its endocrine function.
Sample Metadata Fields
Sex, Specimen part
View Samples