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SRP109291
Mus musculus
35 Downloadable Samples
Illumina HiSeq 2500, Illumina HiSeq 3000
Description
To understand the extent of Smad-mediated gene regulation in the colon, we isolated colon epithelium from Smad4?Lrig1 and from Smad4+ control mice (either mice lacking a CreERT allele and treated with tamoxifen, or mice bearing a CreERT allele but treated with vehicle only) and analyzed the colonic epithelium by RNAseq. The ability of TGFß1 and/or BMP2 to block TNF-mediated induction of Ccl20 from our study suggests that these Smad-mediated pathways may act as gatekeepers for induction of other inflammation-associated genes. To determine if Smad-mediated signaling blocks all or specific subsets of TNF-induced genes, we analyzed both colonocytes and mouse colonoid treated with or without TNF, TGFß1, and BMP2 by RNA seq. Overall design: In total, three RNAseq experiments were performed and three biological replicates were used for each condition: 1. Colon epithelium from Smad4?Lrig1 and from Smad4+ control mice was isolated. Total RNA was isolated from these tissues using RNeasy kit (Qiagen). Processing of RNA using a TruSeq Stranded mRNA sample prep kit was conducted according to the manufacturer's instructions (Illumina, San Diego, CA). 32~37 million 51 base pair single-end reads were generated per sample. 2. Total RNA was isolated from colonocytes treated with or without TNF, TGFß1, and BMP2 using RNeasy kit (Qiagen). Processing of RNA using a TruSeq Stranded mRNA sample prep kit was conducted according to the manufacturer's instructions (Illumina, San Diego, CA). 26~50 million 75 base pair paired-end reads were generated per sample. 3. Total RNA was isolated from mouse colonoid treated with or without TNF, TGFß1, and BMP2 using RNeasy kit (Qiagen). Processing of RNA using a TruSeq Stranded mRNA sample prep kit was conducted according to the manufacturer's instructions (Illumina, San Diego, CA). 50~72 million 75 base pair paired-end reads were generated per sample.
Publication Title
Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Previously we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-green fluorescent protein (RUC-GFP) fusion, b-galactosidase, and b-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase, TK), and A56R (encoding hemagglutinin, HA) loci of the viral genome, respectively. Intravenous (i.v.) injections of GLV-1h68 (1 107 pfu/mouse) into nude mice with established (500 mm3) subcutaneous (s.c.) GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity and oncolytic efficacy. GLV-1h68 demonstrated an enhanced tumor targeting specificity and much reduced toxicity compared to its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.
Publication Title
Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 6 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
RNase Y of Bacillus subtilis is a key member of the degradosome and important for bulk mRNA turnover. In contrast to B. subtilis, the RNase Y homologue (rny/cvfA) of Staphylococcus aureus is not essential for growth. Here we found that RNase Y plays a major role in virulence gene regulation. Accordingly, rny deletion mutants demonstrated impaired virulence in a murine bacteraemia model. RNase Y is important for the processing and stabilisation of the immature transcript of the global virulence regulator system SaePQRS. Moreover, RNase Y is involved in the activation of virulence gene expression at the promoter level. This control is independent of both the virulence regulator agr and the saePQRS processing and may be mediated by small RNAs some of which were shown to be degraded by RNase Y. Besides this regulatory effect, mRNA levels of several operons were significantly increased in the rny mutant and the half-life of one of these operons was shown to be extremely extended. However, the half-life of many mRNA species was not significantly altered. Thus, RNase Y in S. aureus influences mRNA expression in a tightly controlled regulatory manner and is essential for coordinated activation of virulence genes.
Publication Title
RNase Y of Staphylococcus aureus and its role in the activation of virulence genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 6 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
For Staphylococcus aureus it was shown previously that aminocoumarinecoumarin antibiotics such as novobiocin lead to immediate down-regulation of recA expression and thereby inhibition of the SOS response, the mutation frequency and the recombination capacity. Aminocoumarinecoumarin function by inhibition of the ATPase activity of the gyrase subunit B. Here we analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. By use of a novobiocin resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and Northern blot hybridization revealed that the expression of a distinct set of genes is increased (e.g. recF-gyrB-gyrA, rib operon and ure operon )), or decreased (e.g. arlRS, recA, lukA, hlgC, fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the supercoiling level in S. aureus. Thus, down-regulation of arlRS might in part compensate for the relaxing effect of novobiocin. Novobiocin resulted in down-regulation of several of arlRS repressed target genes in an arl mutant. Global analysis and gene mapping of supercoiling sensitive genes did not give indications that they are clustered in the genome. Promoter fusion assays confirmed that responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. The results indicate that molecular property of the spacers of a given promoter dictatesa given promoter rather than chromosomal topology dictates the responsiveness towards changes in supercoiling rather than chromosomal topology.
Publication Title
Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
RNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133Plus 2.0 arrays were hybridized with probe from total RNA isolated from blood sampled from 6 umbilical cords and 6 healthy adult humans.
Publication Title
Let-7 microRNAs are developmentally regulated in circulating human erythroid cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells.
Publication Title
BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
RCC cells (786-O) were transfected with VHL. The parental cell line should be compared to the transfectant (+VHL) under nomoxia as well as under hypoxia conditions.
Publication Title
Distinct von Hippel-Lindau gene and hypoxia-regulated alterations in gene and protein expression patterns of renal cell carcinoma and their effects on metabolism.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Inflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis.
Publication Title
MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Myeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions.
Publication Title
IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse CD8+ T cells affected by ID3 (Inhibitor of DNA binding 3) display patterns of gene expression suggesting enhanced persistance and survival. In this study, we identified genes differentially expressed between ID32a transduced and mock transduced, and ID32a knockout and wild type mouse CD8+ T cells. Most prominent functions of differentially expressed genes include DNA replication-associated repair, maintenance of chromosome stability and mitotic cell divison machinery. Overall, these data suggest that ID3 acts in favor of maintained survival in CD8+ mouse T cells.
Publication Title
Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells.
Sample Metadata Fields
Treatment
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