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GSE51925
Mus musculus
33 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Old C57BL/6 mice cannot mount an effective innate immune response
Publication Title
Aged mice are unable to mount an effective myeloid response to sepsis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles.
Publication Title
A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Diclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as model eukaryote to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. Especially pleiotropic drug resistance genes and genes under control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as well as zinc-responsive genes.
Publication Title
Involvement of the pleiotropic drug resistance response, protein kinase C signaling, and altered zinc homeostasis in resistance of Saccharomyces cerevisiae to diclofenac.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 69 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The polytrauma (PT) murine model has unique transcriptomic responses 2 hrs, 1 day and 3 days after injury. We determined with this clinically relevant model that the increased morbidity in the elderly is secondary to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an 'emergency myelopoietic' response, engendering myeloid cells that fail to clear secondary infection. In addition, the elderly appear unable to effectively resolve their inflammatory response to severe injury.
Publication Title
A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
Context: Despite the well-recognized clinical features due to insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues. objective: To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of TRa-expressing cells. Methods: We performed next-generation RNA sequencing on whole blood samples from 8 athyroid patients (4 females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene co-expression network analysis (WGCNA) was applied to identify thyroid state-related networks. Results: We detected 486 differentially expressed (DE) genes (fold-change above 1.5; multiple testing corrected P-value <0.05), of which 76 % were positively and 24 % were negatively regulated. Gene ontology (GO) enrichment analysis revealed that 3 biological processes were significantly overrepresented of which the process translational elongation showed the highest fold enrichment (7.3 fold, P=1.8 x 10-6). Comparative transcriptome analysis revealed significant overlap with DE-genes in muscle samples upon different thyroid state (1.7-fold enrichment; P=0.02). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO-analysis suggested that thyroid state regulates platelet function. Conclusions: Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRa-expressing leukocytes. In addition, TH may regulate gene expression in platelets. Whole blood samples might potentially be used as a proxy for other TRa-expressing tissues in humans. Overall design: Transcriptome profiling (RNA-Seq) of 8 thyroidectomized human whole blood samples, sequenced first in hypothyroid state and after levothyroxine supplementation sequenced in a hypothyroid (mild thyreotoxic state) state on a Illumina HiSeq 2500 system.
Publication Title
Thyroid State Regulates Gene Expression in Human Whole Blood.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ and CD141+ myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for CD1c+ and CD141+ was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady-state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases.
Publication Title
Human Bone Marrow-Derived Myeloid Dendritic Cells Show an Immature Transcriptional and Functional Profile Compared to Their Peripheral Blood Counterparts and Separate from Slan+ Non-Classical Monocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Abstract: Human 6-sulfo LacNac (slan)+ cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DC. To gain deeper insight into the functional specialization of slan+ cells, we have compared them with both conventional myeloid DC subsets (CD1c+ and CD141+) in human peripheral blood. Using genome-wide transcriptional profiling as well as extensive functional tests, we clearly show that slan+ cells form a distinct, non-DC-like, population. They cluster away from both DC subsets and their gene expression profile evidently suggests involvement in distinct inflammatory processes. An extensive comparison with existing genomic data sets also strongly confirmed the relationship of slan+ with the monocytic compartment rather than with DC. From a functional perspective, their ability to induce CD4+ and CD8+ T cell proliferation is relatively low. Combined with the finding that antigen presentation by MHC class II is at the top of under-represented pathways in slan+ cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression of complement receptors on their cell surface, together with their high secretion of IL-1 and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies.
Publication Title
Transcriptional profiling reveals functional dichotomy between human slan<sup>+</sup> non-classical monocytes and myeloid dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 14 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The intercalated disc of cardiac myocytes is emerging as a crucial structure in the heart. Loss of intercalated disc proteins like N-cadherin causes lethal cardiac abnormalities, mutations in intercalated disc proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein-2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the intercalated disc, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated b-catenin to cadherin, while overexpression of LIMP-2 has the opposite effect. Taken together, our data show that lysosomal integrated membrane protein-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the intercalated disc.
Publication Title
Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Prdx2 is the thioredoxin-dependent peroxidase that reduces H2O2 using reducing power NADPH in the presence of thioredoxin and thioredoxin reductase. Prdx2 plays an important role in growth. factor signaling in mammlian cells. Therefore, we examined the gene expression in colon adenocarcinoma cell line HT29 after Prdx2 depletion. Prdx2 depletion resulted in a significant alteration on gene expression, including protein synthesis, metabolisms, and cell cycle. Overall design: Control-siRNA-transfected versus PRDX2-siRNA-transfected HT29 and SW480 cells
Publication Title
Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
RNAi mediated knockdown of BTG1 in the acute lymphoblastic cell line RS4;11 causes this cell line to become resistant to prednisolone treatment when compared to control cells.
Publication Title
BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples