Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Sex, Age
View SamplesAnalysis of the effect on global gene regulation in epididymal adipose tissue of overexpressing the cytoskeletal tropomyosin, Tm5NM1 to help understand the transcriptional events that lead to increased fat mass in transgenic mice.
Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments.
Specimen part
View SamplesData present the expression analysis of different mouse ES cell line with altered expression of GTF2I.
TFII-I regulates target genes in the PI-3K and TGF-β signaling pathways through a novel DNA binding motif.
Specimen part
View SamplesGlycolytic Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of glyceraldehyde 3-phospate to 1,3-bisphosphoglycerate by coupling with the reduction of NAD+ to NADH. We generated mutants of the Arabidopsis plastidial GAPDH isoforms (At1g79530, At1g16300; GAPCp1, GAPCp2). gapcp double mutants (gapcp1 gapcp2) display a drastic phenotype of arrested root development and sterility.Complex interactions occurring between ABA and sugar signal transduction pathways have been shown, but the molecular mechanisms connecting both pathways are not well understood. Since we found drastic carbohydrate changes in gapcp1 gapcp2, we studied their response to ABA. by performing a microarray analysis comparing gapcp1 gapcp2 and wild type seedlings after a long term treatment with ABA.
Arabidopsis plants deficient in plastidial glyceraldehyde-3-phosphate dehydrogenase show alterations in abscisic acid (ABA) signal transduction: interaction between ABA and primary metabolism.
Specimen part, Treatment
View SamplesStreptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFN was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFN-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFN in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China.
Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.
Sex, Specimen part
View SamplesStreptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFN was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFN-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFN in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China.
Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.
Sex, Specimen part
View SamplesStreptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFN was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFN-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFN in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China.
Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.
Sex, Specimen part
View SamplesOSM increases the antiviral effect of IFN in Huh7 cells infected with hepatitis A virus (HAV) or HCV replicon and synergizes with IFN in the induction of antiviral genes
Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells.
No sample metadata fields
View SamplesActinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood.
Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel.
Specimen part, Disease, Disease stage, Subject
View SamplesHepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array RT PCR. The expression of the best 45 genes was then investigated in human samples resulting in 18 genes which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodelling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.
A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.
Specimen part
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