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SRP095866
Mus musculus
22 Downloadable Samples
Ion Torrent Proton
Description
We designed a study to investigate immunoediting of an epithelial cancer genome using wildtype and immunodeficient mice, NGS, and analytical pipelines to process and analyze the data. We carried out experiments with wildtype and immunodeficient RAG1-/- mice with transplanted tumors and analyzed longitudinal samples with respect to the genomic landscape and the immunophenotypes of the tumors. Finally, we performed also experiments with anti-PD-L1 antibodies and show how the activation of the PD1-PD-L1 axis modulates immunoediting. MC38 cells were subcutaneously injected into wild-type C57Bl/6 and immunodeficient Rag1-/- mice. Samples were taken at predefined time points and subjected to detailed analysis, including FACS, exome sequencing, RNA sequencing and SNP arrays. Overall design: Samples were taken at predifined time points, in triplicates and subjected to RNA sequencing using Ion Torrent Proton
Publication Title
Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
A basal (MDAMB468) and luminal (ZR75-1) cell line were treated with DMSO or PKC412 for 6h Overall design: 2 DMSO and 3 PKC412 treated samples for each cell line
Publication Title
Targeting a cell state common to triple-negative breast cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Human cell line HCT116 incubated with Myxothiazol for 5 or 17 hours
Publication Title
A sustained deficiency of mitochondrial respiratory complex III induces an apoptotic cell death through the p53-mediated inhibition of pro-survival activities of the activating transcription factor 4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ly6Chi monocytes massively infiltrate the CRC-tumors by virtue of their CCR2 expression and further mature into Ly6CloF4/80hi CD64hiMHCII+ TAM upon tumor progression. We demonstrated that TAM-deficient tumors display impaired tumor-growth via alternation of the ECM morphology, structure and composition. Using advanced high-resolution optical imaging to visualize the tumoral-ECM macromolecule network together with transcriptomic and proteomic approaches we unraveled that TAM play critical role in the deposition, linearization and cross-linking of collagenous ECM. Remarkably, we show that cues embedded in ECM by TAM-mediated remodeling activity promote tumor cell proliferation in vitro and orthotopic tumor development in vivo.
Publication Title
Tumor macrophages are pivotal constructors of tumor collagenous matrix.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
The balance between protecting tissue integrity and efficient immune response is critical for host survival. Here we investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection using a combined genomic and proteomic approach. We followed the transcriptional dynamics and ECM- related responses in a mouse model of influenza virus infection, integrated with whole tissue imaging and functional assays. Our study identifies MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza virus infection. We show that selective inhibition of MT1-MMP-driven ECM proteolysis protects the tissue from infection-related structural and compositional damage. Inhibition of MT1-MMP did not significantly alter the immune response or cytokine expression, indicating its dominant role in ECM remodeling. We demonstrate that the available treatment for influenza virus (Tamiflu/ Oseltamivir) does not prevent lung ECM damage and is less effective than anti-MT1-MMP treatment in influenza virus and Streptococcus pneumoniae coinfection paradigms. Importantly, combination therapy of Tamiflu with anti-MT1-MMP shows a strong synergistic effect and results in complete recovery in mice. This study highlights the importance of tissue tolerance agents for surviving infectious diseases, and the potential of such host-pathogen therapy combination for respiratory infections. Overall design: Overall 8 samples were included, in duplicates, both infected and non-infected control cells were includeda. Both MT1-MMP positive and MT1-MMP negative were tested were non-infectdd, MT1-MMP negative cells served as controls.
Publication Title
Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 1000
Description
The nuclear factor-kB (NF-kB) family of transcription factors is important for hematopoietic function, including development, maintenance, and differentiation of different hematopoietic lineages in response to cytokines and infection. Although ligand-independent or basal NF-kB signaling is required for HSC homeostasis in the absence of inflammation, the upstream tonic mediators of NF-kB signaling are not known. Herein we describe TNF receptor associated factor 6 (TRAF6) as an essential regulator of HSC homeostasis by preserving self-renewal and quiescence through basal activation of NF-kB. Hematopoietic-specific deletion of Traf6 resulted in impaired HSC self-renewal and fitness. Gene expression, RNA splicing, and molecular analyses of Traf6-deficient HSPC revealed changes in adaptive immune signaling, innate immune signaling, and NF-kB signaling, indicating that signaling via TRAF6 in the absence of cytokine stimulation and/or infection occurs in HSPC and is required for HSC function. In addition, we established that loss of NF-kB signaling is responsible for the major hematopoietic defects observed in Traf6-deficient HSPC as deletion of IKKb similarly resulted in impaired HSC self-renewal and fitness. Taken together, our observations position TRAF6 as an essential regulator of HSC homeostasis by maintaining a minimal threshold level of IKKb/NF-kB signaling. Overall design: Hematopoietic stem and progenitor cell (HSPC)-enriched lineage-Sca1+Kit+ (LSK) cells were sorted from mice reconstituted with Vav-Cre+ and Traf6-/-;Vav-Cre+ bone marrow cells. Total RNA was extracted from LSK cells and purified with Quick-RNA MiniPrep Kit (Zymogen). RNA quality was determined using the Agilent Bioanalyzer 2100 (Hewelett Packard). 100 ng total RNA was used for enrichment of poly A RNA with the Apollo 324 (WaferGen, Fremont, CA). Poly A RNA was further fragmented (RNase III), adaptor-ligated, and reverse transcribed (Superscript III reverse transcriptase, Lifetech, Grand Island, NY), followed by purification using Agencourt AMPure XP beads (Beckman Coulter, Indianapolis IN). To prepare libraries, universal and index-specific primers, and sample-specific index were added to each adaptor-ligated cDNA sample to amplify the library, followed by purification using AMPure XP beads. The quality and yield of the libraries were assessed on the Bioanalyzer (Agilent, Santa Clara, CA). Libraries at the final concentration of 15 pM were clustered onto a PE flow cell using Illumina''s TruSeq PE Cluster kit v3, and sequenced using TruSeq SBS kit on the Illumina HiSeq system. To study differential gene expression, individually indexed libraries were proportionally pooled (20-50 million reads per sample in general) for clustering in cBot system (Illumina, San Diego, CA). Libraries at the final concentration of 15 pM were clustered onto a single read (SR) flow cell using Illumina's TruSeq SR Cluster kit v3, and sequenced for 50 bp using TruSeq SBS kit on Illumina HiSeq system.
Publication Title
TRAF6 Mediates Basal Activation of NF-κB Necessary for Hematopoietic Stem Cell Homeostasis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 46 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The goal of this study was to examine whether immune responses to Plasmodium chabaudi infection differ between the sexes and are altered by the presence of gonadal steroids. Gonadally-intact males were more likely than intact females to die following P. chabaudi infection, exhibit slower recovery from infection-associated weight loss, hypothermia, and anemia, have reduced IFN-associated gene expression and IFN production during peak parasitemia, and produce less antibody during the recovery phase of infection. Gonadectomy of male and female mice altered these sex-associated differences, suggesting that sex steroid hormone, in particular androgens and estrogens, may modulate immune responses to infection.
Publication Title
Involvement of gonadal steroids and gamma interferon in sex differences in response to blood-stage malaria infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng. Additional time points during transformation and activation were sequenced as well, but not assayed for expression.
Publication Title
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes
Publication Title
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
Sample Metadata Fields
No sample metadata fields
View Samples