Cardiomyopathy in type 1 diabetic patients is characterized by early onset diastolic and late onset systolic dysfunction. The mechanism underlying development of diastolic and systolic dysfunction in diabetes remains unknown.
Activation of a novel long-chain free fatty acid generation and export system in mitochondria of diabetic rat hearts.
Age
View SamplesWe compared the gene expression in roots between WT and uri mutant under +Fe and -Fe conditions using ATH1 microarray analysis to explore which genes are affected by the loss of URI function.
The iron deficiency response in <i>Arabidopsis thaliana</i> requires the phosphorylated transcription factor URI.
Specimen part
View SamplesRecent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs), as markers for melanoma stem or initiating cells. Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy. Overall design: RNA-seq of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively.
Pseudotime Dynamics in Melanoma Single-Cell Transcriptomes Reveals Different Mechanisms of Tumor Progression.
Specimen part, Subject
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 SamplesThe goal of the microarray experiment was to identify genes that were differentially expressed in NAD-treated and water-treated sweet orange leaf tissues. Results indicated that, compared with the water treatment, the NAD tretament triggered profound transcriptome changes in the citrus leaves, with about 1,200 genes being up-regulated or down-regulated by twofold or more.
Exogenous Nicotinamide Adenine Dinucleotide Induces Resistance to Citrus Canker in Citrus.
Specimen part, Time
View SamplesMicroarray analysis of microglia in a mouse model of amyotrophic lateral sclerosis identified the dysregulation of Brca1.
Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS.
Specimen part
View SamplesSCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors.
Genetic interaction between Kit and Scl.
Cell line, Treatment
View SamplesThis study aims at isolate a subpopulation of thymic epithelial cells (TECs) enrich in thymic epithelial progenitors. While recent studies have shown that bipotent TEC progenitors exist in adults, the identity of thymic epithelial progenitors (TEPCs) is still debated. Using an exclusively in vivo approach, we show that quiescent UEA1– TECs actively proliferate during thymic regeneration in 6-month-old mice and possessed a MHCIIlo Sca1hi CD49fhi CD24lo Plet1– phenotype. We then performed RNA sequencing of UEA1- quiescent (label-retaining cells, called LRCs) cells and compared them to UEA1- GFP- (nonquiescent, NonLRCs) TECs. Overall design: We analyzed 2 samples with one replicate each. Each sample contains pooled cells isolated from 11 mice to reach a minimum of 10000 cells/replicate.
Detection of Quiescent Radioresistant Epithelial Progenitors in the Adult Thymus.
Specimen part, Subject
View Samples