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GSE104063
Mus musculus
46 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study gut microbiota from young or old conventional mice was transferred to young germ-free mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyers patches, and mesenteric lymph nodes from conventionalized germ-free mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here we show by transferring aged microbiota to young germ-free mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the germ-free mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young germ-free mice.
Publication Title
Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 30 Downloadable Samples
Illumina HiSeq 2000
Description
HIV-1 nucleoside reverse transcriptase inhibitor (NRTI) use is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to NRTIs has predominantly been assigned to mitochondrial polymerase-? inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of these drugs, which are rarely discussed in the literature, include direct inhibition of the mitochondrial respiratory chain (MRC), decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC), which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure. Overall design: RNA-seq on Caenorhabditis elegans exposed to DMSO, 3''-azido-3''-deoxythymidine (zidovudine or AZT), 2'',3''-didehydro-2'',3''-deoxythymidine (stavudine or d4T), 3''-deoxy-3''-fluorothymidine (alovudine or FLT) or untreated control after 24 or 72 hours of exposure.
Publication Title
Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression.
Publication Title
Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
A specialized population of memory CD8+ T-cells resides in the epithelium of the respiratory tract to maintain protection against recurring infections. These cells express CD69 and the integrin 7 (CD103) and correspond to tissue resident memory T-cells (TRM) also described in intestine, liver and brain. A less well characterized population of CD103- CD8+ T-cells also resides in lungs and expresses markers characteristic of effector memory T-cells (TEM). We determined the transcriptional profiles of these memory CD8+ T-cell subsets retrieved from human lung resection samples and compared these with corresponding T-cell populations from peripheral blood of the same individuals. Our results demonstrate that each of the populations exhibits a distinct transcriptional identity. We found that the lung environment has a major impact on gene expression profiles. Thus, transcriptomes from CD103+ and CD103- subsets from lungs are much more resemblant to one another than to those from CD103+ or CD103- memory CD8+ T-cells from blood. TRM express specific sets of chemokine receptors, in accordance with their unique migratory properties. Furthermore, these cells constitutively express cytokine and cytotoxic genes for immediate effector function and chemokines to attract auxiliary immune cells. At the same time, multiple genes encoding inhibitory regulators are also expressed. This suggests that rapid ability to unleash effector functions is counterbalanced by programmed restraint, a combination that may be critical in the exposed but delicate tissue of the lung. Comprehensive sets of transcription factors were identified that characterize the memory CD8+ populations in the lungs. Prominent among these were components of the Notch pathway. Using mice genetically lacking expression of the NOTCH1 and NOTCH2 receptors in T-cells, we demonstrated that Notch controls both the number of lung TRM as well as the function of lung TEM. Our data illustrate the adaptation of lung resident T-cells to the requirements of the respiratory epithelial environment. Defining the molecular imprinting of these cells is important for rational vaccine design and may help to improve the properties of T-cells for adoptive cellular therapy.
Publication Title
Programs for the persistence, vigilance and control of human CD8<sup>+</sup> lung-resident memory T cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- IlluminaHiSeq2000
Description
Goal of this study is to identify the transcriptome of human male germ cell subtypes during normal spermatogenesis as a reference for subfertility.
Publication Title
Unraveling transcriptome dynamics in human spermatogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Protective interactions with bystander cells in micro-environmental niches such as lymph nodes (LNs) contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of BCL-2 family members. Pro-survival proteins BCL-XL, BFL-1, and MCL-1 are upregulated by LN-residing T cells through CD40L interaction, presumably via NF-B signaling. Macrophages also reside in the LN, and are assumed to provide important supportive functions for CLL cells. However, if and how macrophages are able to induce survival is incompletely known. We first established that macrophages induced survival due to an exclusive upregulation of MCL-1. Next, we investigated the mechanism underlying MCL-1 induction by macrophages in comparison with CD40L. Genome-wide expression profiling of in vitro macrophage- and CD40L-stimulated CLL cells indicated activation of the PI3K-AKT-mTOR pathway, which was confirmed in ex vivo CLL LN material. Inhibition of PI3K-AKT-mTOR signaling abrogated MCL-1 upregulation and survival by macrophages as well asCD40 stimulation. MCL-1 can be regulated at multiple levels, and we established that AKT leads to increased MCL-1 translation, but does not affect MCL-1 transcription or protein stabilization. Furthermore, among macrophage-secreted factors that could activate AKT, we found that induction of MCL-1 and survival critically depended on C-C Motif Chemokine Receptor-1 (CCR1). In conclusion, this study indicates that two distinct micro-environmental factors, CD40L and macrophages, signal via CCR1 to induce AKT activation resulting in translational stabilization of MCL-1, and hence can contribute to CLL cell survival.
Publication Title
Macrophages confer survival signals via CCR1-dependent translational MCL-1 induction in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
To provide further insight about the effects of prolonged Ezh2 inhibition in glioblastoma using preclinical mouse models and doxycycline-inducible shRNAs that mimic the effects of a selective EZH2 inhibitor. We demonstrate that prolonged Ezh2-depletion causes a robust switch in cell fate, including significantly enhanced proliferation and DNA damage repair and activation of part of the pluripotency network, resulting in altered tumor cell identity and tumor progression. Overall design: SVZ derived neural stem cells (NSCs) were isolated from 7 days old p53;Ink4a/Arf;Krasv12;LucR compound conditional mice and cultured in NSC specific serum-free medium supplemented with 20ng/ml of both EGF and bFGF (R&D systems). NSCs were grown adhesion-free for the first passages to eliminate non-sphere-forming cells. Next, cells were grown adherent on poly-L-Ornithine and Laminin plates and three times infected with lentiviral CMV-Cre. These floxed, tumorigenic cells are further referred as glioma initiating cells (GICs). Next, GICs were infected with a tet-inducible, doxycycline-responsive short hairpin construct (FH1-tUTG-shEzh2). After FACS sorting for GFP, GICs were injected intracranial in NOD-SCID mice and treated with or without doxycycline in the drinking water
Publication Title
Prolonged Ezh2 Depletion in Glioblastoma Causes a Robust Switch in Cell Fate Resulting in Tumor Progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Overexpression of miR-9 and miR-9* in 32D cells, cells grown under IL-3 conditions and miR-9 and miR-9* were introduced with retroviral vectors containing about ~150 bp up and downstream of mmu-mir-9-2.
Publication Title
Aberrant expression of miR-9/9* in myeloid progenitors inhibits neutrophil differentiation by post-transcriptional regulation of ERG.
Sample Metadata Fields
Cell line
View Samples- Hordeum vulgare, Hordeum vulgare subsp. spontaneum
- 18 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
The bird cherry-oat aphid (Rhopalosiphum padi L.) (Homoptera: Aphididae) is an important pest on cereals causing plant growth reduction but no specific leaf symptoms. Breeding of barley (Hordeum vulgare L.) for R. padi resistance shows that there are several resistance genes involved, reducing aphid growth. In an attempt to identify candidate sequences for resistance-related genes, we performed a microarray analysis of gene expression after two days of aphid infestation in two susceptible barley lines and two genotypes with partial resistance. One of the four lines is a descendant of two of the other genotypes. The analysis revealed large differences in gene induction between the four lines, indicating substantial variation in response even between closely related genotypes. Genes induced in the aphid-infested tissue were mainly related to defence, primary metabolism and signalling. Only twenty-four genes were induced in all lines, none of them related to oxidative stress or secondary metabolism. Few genes were down-regulated and none of those was common to all four lines. There were differences in aphid-induced gene regulation between resistant and susceptible lines, and results from control plants without aphids also revealed differences in constitutive gene expression between the two types of lines. Candidate sequences for both induced and constitutive resistance factors have been identified, among them a proteinase inhibitor, a Ser/Thr kinase and several thionins.
Publication Title
Microarray analysis of the interaction between the aphid Rhopalosiphum padi and host plants reveals both differences and similarities between susceptible and partially resistant barley lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
Type 2 Diabetes, obesity and metabolic syndrome are pathologies impacting a large population worldwide where insulin resistance plays a central role. These pathologies are usually associated to a dysregulation of insulin secretion leading to a chronic exposure of the tissues to high insulin levels (i.e. hyperinsulinemia) what diminishes the concentration of key downstream elements causing insulin resistance. The complexity of the study of insulin resistance relies on the heterogeneity of the metabolic states where it’s observed. In consequence, animal models for the study of insulin resistance, can not completely recapitulate the metabolic status of insulin resistant humans, what is translated in contradictory observations. To contribute to the understanding of the mechanisms triggering insulin resistance we have developed a zebrafish model to study insulin metabolism and its associated disorders. Zebrafish embryos appeared to be sensitive to human recombinant insulin, becoming insulin resistant when exposed to a high dose of the hormone, as confirmed by glucose measurements. Moreover RNAseq-based transcriptomic profiling of these embryos revealed a strong down regulation of a number of immune relevant genes as a consequences of the exposure to hyperinsulinemia. Interestingly, as an exception, the negative immune modulator ptpn6 appeared to be up regulated in insulin resistant embryos. Knockdown of ptpn6 showed to counteract the observed down regulation of the immune system and insulin signalling pathways effects at the transcriptional level caused by hyperinsulinemia. These results show that ptpn6 is a mediator of the metabolic switch between insulin sensitive and insulin resistant states. Our zebrafish model for hyperinsulinemia has therefore demonstrated it suitability to discover novel regulators of insulin resistance. In addition, our data will be very useful to further study the function of immunological determinants in a non-obese model system. Overall design: 16 samples in total were analyzed. 4 replicates from control samples (injected with PBS) and 4 replicates of insulin injected samples at 0.5 hpi and 4 hpi. In each sample 10 embryos were pooled.
Publication Title
Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples