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GSE47406
Staphylococcus aureus
18 Downloadable Samples
Affymetrix S. aureus Genome Array (saureus)
Description
Staphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from patients with chronic S. aureus infections after long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In TD-SCVs, mutations of thymidylate synthase (thyA, TS), essential for DNA synthesis, occur. However, it has never been shown, that TMP-SMX is responsible for the induction and selection of TD-SCVs. Short-term exposure of TMP-SMX induced the TD-SCV phenotype morphologically as shown in transmission electron-microscopy and on the transcriptional level by qRT-PCR in wild-type S. aureus, while selection of TD-SCVs with thyA mutations occurred only rarely after long-term exposure. In reversion experiments with clinical TD-SCVs, all revertants revealed compensating mutations at the initially identified mutation site. Whole DNA microarray analysis of a thyA deletion mutant (thyA), which exhibited the typical TD-SCV phenotype, identified tremendous alterations compared to the wild-type. Important virulence regulators such as agr, arlRS, sarA and major virulence determinants including hla, hlb, sspA, sspB and geh were down-regulated, while genes associated with the colonization capacity like fnbA, fnbB, spa, clfB, sdrC and sdrD were up-regulated. The expression of genes involved in pyrimidine and purine metabolism as well as in nucleotide interconversion changed significantly. The thyA-mutant was attenuated in virulence in both, a Caenorhabditis elegans killing model and an acute murine pneumonia model. Furthermore, competition experiments in vitro and in vivo (using a chronic pneumonia mouse model) revealed a survival and growth advantage of the thyA-mutant under low thymidine conditions and TMP-SMX exposure. In conclusion, our results clearly show for the first time that TMP-SMX induces the TD-SCV phenotype after short-term exposure in S. aureus and that long-term exposure selects thyA mutations providing an advantage for TD-SCVs under specified conditions. Thus, our results help to understand the dynamic processes of induction and selection of S. aureus TD-SCVs during TMP-SMX exposure.
Publication Title
Inactivation of thyA in Staphylococcus aureus attenuates virulence and has a strong impact on metabolism and virulence gene expression.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
There is an association between transcriptome and the exercise-related phenotype. Peripheral blood cells suffer alterations in the gene expression pattern in response to perturbations caused by exercise. The acute response to endurance activates stress and inflammation, as well as growth and tissue repair responses.
Publication Title
PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Vertebrates typically harbor a rich gastrointestinal microbiota, which has co-evolved with the host over millennia and is essential for several of its physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T helper (Th)17 population in the small intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17-dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type-1 diabetes in this prototypical, spontaneous model. There was a strong co-segregation of SFB-positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T cell compartments of the gut, pancreas or systemic lymphoid tissues. Th17 signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4+ T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, likely reflecting their variable dependence on different Th subsets.
Publication Title
Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 87 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of gene expression over serial 150um sections of a single gestational week 14.5 human neocortical specimen. The hypothesis tested with this dataset was that a transcriptional signature of radial glia (neural stem cells) could be isolated via unsupervised gene coexpression analysis due to variation in the abundance of this cell type from section to section. This dataset is the first of its kind generated using this method (Gene Coexpression Analysis of Serial Sections, or GCASS).
Publication Title
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.
Sample Metadata Fields
Age, Specimen part
View Samples- Bos taurus
- 1 Downloadable Sample
Illumina HiSeq 2000
Description
Sequencing of a pool of 9 bulls of varying conception rate (CR) scores from -2.9 to 3.5.
Publication Title
Cryopreserved bovine spermatozoal transcript profile as revealed by high-throughput ribonucleic acid sequencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 240 Downloadable Samples
- NextSeq500
Description
Long non-coding RNAs (lncRNAs) are a diverse category of transcripts with poor conservation and have expanded greatly in primates, particularly in their brain. We identified a lncRNA, which has acquired 16 microRNA response elements (MREs) for miR-143-3p in the Catarrhini branch of primates. This lncRNA termed LncND (neuro-development) gets expressed in neural progenitor cells and then declines in mature neurons. Binding and release of miR-143-3p, by LncND, can control the expression of Notch. Its expression is highest in radial glia cells in the ventricular and outer subventricular zones of human fetal brain. Down-regulation of LncND in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p over-expression and supported by RNA-seq analysis. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling in the expansion of the neural progenitor pool of primates and hence contributing to the rapid growth of the cerebral cortex. Overall design: Cerebral organoids were generated as in Lancaster et al. (Lancaster and Knoblich, 2014). Organoids were dissociated into single cells and captured on C1 Single-Cell Auto Prep Integrated Fluidic Circuit (IFC) (Fluidigm). The RNA extraction and amplification was performed on the chip as described by the manufacturer. We captured 68 single-cells on a C1 Single-Cell Auto Prep System (Fluidigm) and sequenced the RNA on a NextSeq500 System (Illumina) (Pollen et al., 2014). Out of 68 cells, we obtained 60 high quality cells.
Publication Title
A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- NextSeq500
Description
Long non-coding RNAs (lncRNAs) are a diverse category of transcripts with poor conservation and have expanded greatly in primates, particularly in their brain. We identified a lncRNA, which has acquired 16 microRNA response elements (MREs) for miR-143-3p in the Catarrhini branch of primates. This lncRNA termed LncND (neuro-development) gets expressed in neural progenitor cells and then declines in mature neurons. Binding and release of miR-143-3p, by LncND, can control the expression of Notch. Its expression is highest in radial glia cells in the ventricular and outer subventricular zones of human fetal brain. Down-regulation of LncND in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p over-expression and supported by RNA-seq analysis. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling in the expansion of the neural progenitor pool of primates and hence contributing to the rapid growth of the cerebral cortex. Overall design: SHSY5Y cells treated either with miR-143-3p mimic or 100 nM of siRNA specific for LncND were sequenced on NextSeq500 platform. Scrambled siRNA or miRNA sequences were used as a negative control.
Publication Title
A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 117 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the changes in left ventricle mRNA abundance in response to 5/6 nephrectomy surgery Overall design: Ten week old male Sprague Dawley rats were subjected to the excision model of 5/6 nephrectomy (5/6Nx) or sham surgery. Left ventricle tissue was collected 2, 4, 5 or 7 weeks later for mRNAsequencing.
Publication Title
MicroRNA-21 regulates peroxisome proliferator-activated receptor alpha, a molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the changes in left ventricle mRNA abundance in response to miR-21-5p suppression in 5/6 nephrectomized rats. Overall design: Ten week old male Sprague Dawley rats were subjected to the excision model of 5/6 nephrectomy (5/6Nx) surgery. LNA-anti-scrambled or LNA-anti-miR-21-5p was delivered intravenously in 3 daily doses of 1 mg/kg at 1 and 4 weels post-surgery. Left ventricle tissue was collected for mRNA sequencing 7 weeks after surgery.
Publication Title
MicroRNA-21 regulates peroxisome proliferator-activated receptor alpha, a molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Neurons exploit mRNA localization and local translation to spatio-temporally regulate gene expression during development. Local translation and retrograde transport of transcription factors regulate nuclear gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuronal-like cells and of hippocampal neurons. We show that Hmgn5 3UTR drives growth cone localization and translation of a reporter gene, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth while HMGN5 overexpression induces neurite outgrowth and global chromatin decompaction. Interestingly, control of both neurite outgrowth and chromatin structure is dependent on proper growth cone localization of Hmgn5 mRNA. Our results provide the first evidence that mRNA localization and local translation might serve as a mechanism to couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.
Publication Title
Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth.
Sample Metadata Fields
No sample metadata fields
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