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Rattus norvegicus
80 Downloadable Samples
Illumina HiSeq 2000
Description
In this study we tested the ability to predict organ injury from transcriptomics data in Sprague-Dawley rats at early time points after exposure to thioacetmide (8 and 24 hours). We selected thioacetamide, an organosulfur compound extensively used in animal studies as a hepatotoxin and carcinogen for its ability to cause acute liver damage. Overall design: We treated 30 Sprague-Dawley rats with saline solution (control), 25 mg/kg (low dose), and 100 mg/kg (high dose) to produce different degrees of injury. RNA samples for gene expression analysis were collected from the liver, kidney, and heart at 8 and 24 hours. Number of repicates were five.
Publication Title
Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Danio rerio
- 15 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
Our study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
Publication Title
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite their distinct biology, granulosa cell tumours (GCTs) are treated the same as other ovarian tumours. Intriguingly, a recurring somatic mutation in the transcription factor Forkhead Box L2 (FOXL2) 402C>G has been found in nearly all GCTs examined. This investigation aims to identify the pathogenicity of mutant FOXL2 by studying its altered transcriptional targets. The expression of mutant FOXL2 was reduced in the GCT cell line KGN, and wildtype and mutant FOXL2 were overexpressed in the GCT cell line COV434. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2.
Publication Title
The transcriptional targets of mutant FOXL2 in granulosa cell tumours.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The expansion, trafficking and functional effectiveness of adoptively transferred CD8+ T-cells play a critical role in mediating effective anti-tumor immunity. However, the mechanisms which program the highly proliferative and functional state of CD8+ T-cells are not completely understood. We hypothesized that IL-12, a cytokine commonly induced by TLR activation, could enhance T-cell priming by altering responsiveness to antigen and cytokines. Priming of tumor specific CD8+ T-cells in the presence of IL-12 induced the acquisition of a 'polyfunctional' effector response and increased the generation of memory cells. Moreover, IL-12 priming also promoted high levels of the IL-2 receptor alpha-chain (CD25) and robust IL-2 mediated activation of STAT5. This sensitivity to IL-2 translated into enhanced in vivo proliferation of adoptively transferred CD8+ T-cells. Furthermore, real-time, in vivo imaging of T-cell trafficking confirmed the ability of IL-12 priming to drive in vivo proliferation. IL-12 priming enhanced the anti-tumor function of adoptively transferred cells by reducing established subcutaneous tumor burden, and significantly increasing survival in an established intracranial tumor model. Finally, IL-12 priming of human PBMCs generates tumor specific T-cells phenotypically and functionally similar to IL-12 primed Pmel-1 T-cells. These results highlight IL-12 as an important mediator of CD8+ T-cell effector function and anti-tumor immunity.
Publication Title
Enhanced sensitivity to IL-2 signaling regulates the clinical responsiveness of IL-12-primed CD8(+) T cells in a melanoma model.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was confirmed using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 expression without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to separate stem and progenitor cells, RNA-seq identified unique gene signatures for the separate populations which may serve as biomarkers. Pathways enrichment in stem cells identified ribosome biogenesis and membrane estrogen-receptor signaling with NF?B signaling enriched in progenitors and these were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified cancer stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Overall design: Comparing RNA-seq gene profiles in label-retaining prostate stem cells and non-retaining progenitor cells
Publication Title
Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.
Sample Metadata Fields
Specimen part, Subject
View Samples
GSE10710- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Overexpression of a caspase-resistant form of Bcl-2 (D34A) in human umbilical vein endothelial cells (EC) implanted into immunodeficient mice promotes the maturation of human EC-lined microvessels invested by vascular smooth muscle cells (VSMC) of mouse origin. In contrast, EC implants not overexpressing Bcl-2 form only simple, uncoated EC tubes. Here we compare the phenotypes of vessels formed in vivo and the transcriptomes in vitro of EC expressing different forms of Bcl-2. Wild type Bcl-2, like the caspase resistant D34A Bcl-2 mutant, is anti-apoptotic in vitro and promotes VSMC recruitment in vivo, whereas a G145E mutant that has diminished anti-apoptotic activity in vitro does not promote vessel maturation in vivo. The D34A and wild type forms of Bcl-2, but not the G145E mutant form of Bcl-2 significantly regulate RNA transcripts previously associated with EC-VSMC interactions and VSMC biology, including matrix Gla protein, insulin like growth factor binding protein (IGFBP)-2, matrix metaloproteinase-14 (MMP14), ADAM17 and Stanniocalcin-1. These effects of Bcl-2 on the transcriptome are detected in EC cultured as angiogenic 3-D tubes but are attenuated in EC cultured as 2-D monolayers. Bcl-2-regulated transcription in EC may contribute to vascular maturation, and support design of tissue engineering strategies using EC.
Publication Title
Antiapoptotic activities of bcl-2 correlate with vascular maturation and transcriptional modulation of human endothelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Antiphospholipid antibodies, a maternal risk factor for preeclampsia, increase shedding of necrotic trophoblast debris from the placenta, leading to endothelial dysfunction. Using Affymetrix HGU133 Plus 2 microarrays, we found changes in the transcriptome of placental explants treated with antiphospholipid antibodies including seven mRNAs encoding for genes BCL2L1, MCL1, PDCD2L, FASLG, SEMA6A, PRKCE and TRAIL that are involved in the regulation of apoptosis. Quantitative real-time RT-PCR and immunohistochemistry confirmed a reduction in TRAIL expression. These results may help to understand how antiphospholipid antibodies affect trophoblast cell death and how the antibodies could contribute to the pathogenesis of preeclampsia.
Publication Title
Transcriptomic analysis of placenta affected by antiphospholipid antibodies: following the TRAIL of trophoblast death.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Illumina HiSeq 3000
Description
Purpose: The purpose of this study is to measure the changes in liver transcriptome in response to short-term fasting between 7 and 13 h where the rats were dosed with 2 ml/kg of saline vehicle at 0 h Methods: Total RNA was isolated from the liver, using TRIzol Reagent (Thermo Fisher Scientific, Waltham, MA) and the direct-zol RNA Mini Prep kit (Zymo Research, Irvine, CA). The isolated RNA samples were then submitted to the Vanderbilt University Medical Center VANTAGE Core (Nashville, TN) for RNA quality determination and sequencing. Total RNA quality was assessed using a 2100 Bioanalyzer (Agilent, Santa Clara, CA). At least 200 ng of DNase-treated total RNA with high RNA integrity was used to generate poly-A-enriched mRNA libraries, using KAPA Stranded mRNA sample kits with indexed adaptors (Roche, Indianapolis, IN). Library quality was assessed using the 2100 Bioanalyzer (Agilent), and libraries were quantitated using KAPA library Quantification kits (Roche). Pooled libraries were subjected to 75-bp paired-end sequencing according to the manufacturer's protocol (Illumina HiSeq3000, San Diego, CA). Results: No genes were were found to be differentially expressed with a false discovery rate less than 0.1 Conclusions: There were no significant changes in liver gene expression between 7 and 13 h of fasting Overall design: Liver mRNA profiles of 7- and 13-h fasted Sprague-Dawley rats were generated by RNA-seq.
Publication Title
Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Illumina HiSeq 3000
Description
Purpose: The purpose of this study is to measure the changes in liver transcriptome in response to short-term fasting between 5 and 10 h where the rats were dosed with 6 ml/kg of polyethylene glycol vehicle at 0 h Methods: Total RNA was isolated from the liver, using TRIzol Reagent (Thermo Fisher Scientific, Waltham, MA) and the direct-zol RNA Mini Prep kit (Zymo Research, Irvine, CA). The isolated RNA samples were then submitted to the Vanderbilt University Medical Center VANTAGE Core (Nashville, TN) for RNA quality determination and sequencing. Total RNA quality was assessed using a 2100 Bioanalyzer (Agilent, Santa Clara, CA). At least 200 ng of DNase-treated total RNA with high RNA integrity was used to generate poly-A-enriched mRNA libraries, using KAPA Stranded mRNA sample kits with indexed adaptors (Roche, Indianapolis, IN). Library quality was assessed using the 2100 Bioanalyzer (Agilent), and libraries were quantitated using KAPA library Quantification kits (Roche). Pooled libraries were subjected to 75-bp single-end sequencing according to the manufacturer's protocol (Illumina HiSeq3000, San Diego, CA). Results: No genes were were found to be differentially expressed with a false discovery rate less than 0.1 Conclusions: There were no significant changes in liver gene expression between 5 and 10 h of fasting Overall design: Liver mRNA profiles of 5- and 10-h fasted Sprague-Dawley rats were generated by RNA-seq.
Publication Title
Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Maternal IL10 deficiency elevates susceptibility to fetal loss induced by the model Toll-like receptor agonist lipopolysaccharide, but the mechanisms are not well elucidated. Here we show that Il10 null mutant (Il10-/-) mice exhibit altered local T cell responses in pregnancy, exhibiting pronounced hyperplasia in para-aortic lymph nodes draining the uterus with >6-fold increased CD4+ and CD8+ T cells compared with wild-type controls. Amongst these CD4+ cells, Foxp3+ Treg cells were substantially enriched, with 11-fold higher numbers at day 9.5 post coitum (pc). Lymph node hypertrophy in Il10-/- mice was associated with more activated phenotypes in dendritic cells and macrophages, with elevated expression of MHCII, scavenger receptor and CD80. Affymetrix microarray revealed an altered transcriptional profile in Treg cells from pregnant Il10-/- mice, with elevated expression of Ctse (cathepsin E), Il1r1, Il12rb2 and Ifng. In vitro, Il10-/- Treg cells showed reduced steady state Foxp3 expression, and polyclonal stimulation caused greater loss of Foxp3 and reduced capacity to suppress IL17 in CD4+Foxp3- T cells. We conclude that despite a substantially expanded Treg cell pool, diminished stability of Treg cells, increased numbers of effector T cells, and altered phenotypes in dendritic cells and macrophages in pregnancy all potentially confer vulnerability to inflammation-induced fetal loss in Il10-/- mice. These findings suggest a pivotal role for IL10 in facilitating robust immune protection of the fetus from inflammatory challenge and suggest IL10 deficiency could contribute to human gestational disorders where altered T cell responses are implicated.
Publication Title
Unstable Foxp3+ regulatory T cells and altered dendritic cells are associated with lipopolysaccharide-induced fetal loss in pregnant interleukin 10-deficient mice.
Sample Metadata Fields
Specimen part
View Samples