Filters
Technology
Platform
GSE20390
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selenium has cancer preventive activity that is mediated, in part, through selenoproteins. The role of the 15 kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with shRNA constructs targeting Sep15. Metabolic 75Se-labeling and Northern and Western blot analyses revealed that more than 90% of Sep15 was knocked down. Growth of the resulting Sep15-deficient CT26 cells was reduced (p<0.01) and cells formed significantly (p<0.001) fewer colonies in soft agar compared to control CT26 cells. Whereas most (14/15) BALB/c mice injected with control cells developed tumors, few (3/30) mice injected with Sep15 knockdown cells developed tumors (p<0.0001). The ability to form pulmonary metastases had similar results. Mice injected with the plasmid-transfected control cells had >250 lung metastases/mouse; however, mice injected with the Sep15 knockdown cells only had 7.8 +/- 5.4 metastases. To investigate molecular targets affected by Sep15 status, gene expression patterns between control and knockdown CT26 cells were compared. Ingenuity Pathways Analysis was used to analyze the 1045 genes that were significantly (p<0.001) affected by Sep15 deficiency. The highest scored biological functions were cancer and cellular growth and proliferation. Consistent with these observations, subsequent analyses revealed a G2/M cell cycle arrest in Sep15 CT26 knockdown cells. In contrast, to CT26 cells Sep15 knockdown in Lewis Lung Carcinoma (LLC1) cells did not affect anchorage-dependent or independent cell growth. These data suggest tissue specificity in the cancer protective effects of Sep15 knockdown, which are mediated, at least in part, by influencing the cell cycle.
Publication Title
Deficiency in the 15-kDa selenoprotein inhibits tumorigenicity and metastasis of colon cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparative analysis of gene expression in bone marrow-derived macrophages (BMDM) from trsp knockout mice (Trspfl/fl-LysM-Cre+/-) and Control (Trspfl/fl-LysM-Cre-/-) mice.
Publication Title
Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selenoproteins mediate the cancer-preventive properties of the essential nutrient selenium, but also have cancer-promoting effects. We examined the contributions of the 15-kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and cancer metastasis of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially the interferon-gamma-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient cells. In contrast, the Wnt/Beta-catenin pathway was up-regulated in cells that lacked both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, and controversial results of recent human clinical trials involving dietary selenium, our results are important to general public health.
Publication Title
The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To examine the role of SPS1 in mammals, we generated a Sps1 knockout mouse and found that systemic SPS1 deficiency was embryonic lethal. Embryos were clearly underdeveloped by E8.5 and virtually reabsorbed by E14.5. Removal of Sps1 specifically in hepatocytes using Albumin-cre preserved viability, but significantly affected expression of a large number of mRNAs involved in cancer, embryonic development and the glutathione system. Particularly notable was the extreme deficiency of glutaredoxin 1 (GLRX1) and glutathione-S-transferase omega 1. To assess these phenotypes at the cellular level, we targeted the removal of SPS1 in F9 cells, a mouse embryonal carcinoma cell line, which recapitulated changes in the glutathione system proteins. We further found that several malignant characteristics of SPS1-deficient F9 cells were reversed, suggesting that SPS1 has a role in supporting and/or sustaining cancer. In addition, the increased ROS levels observed in F9 SPS1/GLRX1 deficient cells were reversed and became more like those in F9 SPS1 sufficient cells by overexpressing mouse or human GLRX1. The results suggest that SPS1 is an essential mammalian enzyme with roles in regulating redox homeostasis and controlling cell growth.
Publication Title
Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
NextSeq 500
Description
Selenium, one of a class of selenocysteine-containing proteins (selenoproteins), is an essential micronutrient known for its cancer prevention properties. Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LCMS/ MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels. Overall design: 4 WT zebrafish samples and 4 SepH mutant samples
Publication Title
Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis.
Sample Metadata Fields
Subject
View Samples- Sus scrofa
- 78 Downloadable Samples
- Illumina HiSeq 2500
Description
To optimize the genome annotation, nine tissue and one pool RNA libraries (i.e. heart, liver, spleen, lung, kidney, muscle, fat, ovary, pool.) were constructed using the Illumina mRNA-spleeneq Prep Kit Overall design: We sequenced nine tissues and one pool using illumina Hiseq 2500 platform
Publication Title
Comprehensive variation discovery and recovery of missing sequence in the pig genome using multiple de novo assemblies.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Overall design: Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
Publication Title
Transcriptional reversion of cardiac myocyte fate during mammalian cardiac regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Room temperature whole blood mRNA stabilization procedures, such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable.
Publication Title
Characterization of whole blood gene expression profiles as a sequel to globin mRNA reduction in patients with sickle cell disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ozone is a highly toxic air pollutant and global health concern. Mechanisms of genetic susceptibility to ozone-induced lung inflammation are not completely understood. We hypothesized Notch3 and Notch4 are important determinants of susceptibility to ozone-induced lung inflammation. Wild type (WT), Notch3 (Notch3-/-) and Notch4 (Notch4-/-) knockout mice were exposed to ozone (0.3 ppm) or filtered air for 6-72 hours. Ozone increased bronchoalveolar lavage fluid (BALF) protein, a marker of lung permeability, in all genotypes, but significantly greater concentrations were found in Notch4-/- compared to WT and Notch3-/-. Significantly greater mean numbers of BALF neutrophils were found in Notch3-/- and Notch4-/- mice compared to WT mice after ozone. Expression of whole lung Tnf was significantly increased after ozone in all genotypes, and was significantly greater in Notch3-/- mice compared to WT. Statistical analyses of the transcriptome identified differentially expressed gene networks between WT and knockout mice basally and after ozone, and included Trim30, a member of the inflammasome pathway, and Traf6, an inflammatory signaling member. These novel findings are consistent with Notch3 and Notch4 as susceptibility genes for ozone-induced lung injury, and suggest that Notch receptors protect against innate immune inflammation.
Publication Title
Novel Roles for Notch3 and Notch4 Receptors in Gene Expression and Susceptibility to Ozone-Induced Lung Inflammation in Mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 72 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Liposarcoma is a poorly understood malignancy of fat cells. Lipolysis, a central pathway of adipose tissue metabolism, has been implicated in cancer. Here, we generated tissue-specific single- and combined knockout mice for the two major lipases ATGL and HSL. Notably, double knockout (DAKO) mice developed late onset liposarcoma with complete penetrance, while single knockout mice appeared normal. DAKO whole transcriptome profiles differed from those of single knockout mice, revealing an early-onset tissue-specific response that persisted until the late-onset development of liposarcoma. Cancer-associated markers Gpnmb and G0s2 were among the most highly dysregulated genes in DAKO mice and also in human liposarcomas, suggesting a potential role for these proteins as liposarcoma-specific biomarkers. Taken together, our results demonstrate a novel epistatic interaction linking lipolysis with cancer. DAKO mice provide a promising model for studying early premalignant changes that lead to late-onset disease.
Publication Title
Epistatic interaction between the lipase-encoding genes Pnpla2 and Lipe causes liposarcoma in mice.
Sample Metadata Fields
Age, Specimen part
View Samples