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SRP048707
Mus musculus
15 Downloadable Samples
Illumina HiSeq 1000
Description
Post-transcriptional regulation of mRNA by the RNA binding protein HuR is required in B cells for the germinal centre reaction and for the production of class-switched antibodies in response to T-independent antigens. Transcriptome-wide examination of RNA isoforms, abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interaction, revealed that HuR-dependent mRNA splicing affects hundreds of transcripts including the dihydrolipoyl succinyltransferase (Dlst), a subunit of the aketoglutaratedehydrogenase (aKGDH) enzyme. In the absence of HuR, defective mitochondrial metabolism results in high levels of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for B cell proliferation and differentiation. Overall design: Sequencing analysis of B cell transcriptome using Illumina TruSeq mRNA sample prep kit and Illumina platform. RNA was isolated from ex-vivo or LPS-activated (48h) splenic B cells from HuRflox/flox x mb1wt control or HuRflox/flox x mb1cre mice. 3-4 biological replicates per genotype and condition.
Publication Title
The RNA-binding protein HuR is essential for the B cell antibody response.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 47 Downloadable Samples
- NextSeq 500
Description
Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early response gene activated in the heart under beta-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by NR4A2 expression in cardiomyocytes, and their impact on the physiological response of those cells to sustained beta-adrenergic stimulation. Treatment of adult rat ventricular myocytes (ARVMs) with isoproterenol induced a rapid (< 4 hours) but transient (< 24 hours) increase in NR4A2 expression levels that was accompanied by increased nuclear localization of the transcription factor. Adenovirus-mediated overexpression of NR4A2 modulated the expression of genes linked to adrenoceptor signaling, calcium signaling, cell growth and proliferation, and counteracted the increase in protein synthesis rate and cell surface area mediated by chronic isoproterenol stimulation. In consistence with those findings, NR4A2 overexpression also blocked the phosphorylative activation of ERK1/2, Akt, and of their downstream effector in protein synthesis p70S6K. Prominent among the transcriptional changes induced by NR4A2 was the > 7-fold up-regulation of the dual-specificity phosphatases DUSP2 and DUSP14, two known inhibitors of ERK1/2. Pre-treatment of NR4A2-overexpressing cardiomyocytes with the DUSPs inhibitor BCI prevented the inhibition of ERK1/2 and p70S6K following isoproterenol stimulation. In conclusion, our results suggest that NR4A2 acts as a novel negative feedback regulator of the beta-adrenergic receptor-mediated growth response in cardiomyocytes, and this at least partly through DUSP-mediated inhibition of ERK1/2 signaling. Overall design: Isolated adult rat ventricular myocytes (ARVMs) were transduced at 50 m.o.i. with a recombinant adenovirus containing the full-length cDNA of human NR4A2 under the transcriptional control of the CMV promoter (Vector Biolabs Ad-h-NR4A2; Cat. No: ADV-217057). ARVMs transduced with a recombinant eGFP adenovirus (Vector Biolabs Ad-GFP; Cat. No. 1060) were used as the cell transduction control. At 48 hours post transduction, total RNA was etracted. A total of six independent experiments were performed using ARVMs isolated from different Sprague Dawley rats.
Publication Title
Nuclear receptor subfamily 4 group A member 2 inhibits activation of ERK signaling and cell growth in response to β-adrenergic stimulation in adult rat cardiomyocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Polyamines (putrescine, spermidine, and spermine) are major organic polycations essential for a wide spectrum of cellular processes. The cells require mechanisms to maintain homeostasis of intracellular polyamines to prevent otherwise severe adverse effects. We performed a detailed transcriptome profile analysis of P. aeruginosa in response to agmatine and putrescine with an emphasis in polyamine catabolism. Agmatine serves as precursor compound for putrescine (and hence spermidine and spermine), which was proposed to convert into GABA and succinate before entering the TCA cycle in support of cell growth as the sole source of carbon and nitrogen. Two acetylpolyamine amidohydrolases, AphA and AphB, were identified to be involved in the conversion of agmatine into putrescine. Enzymatic products of AphA were confirmed by mass spectrometry analysis. Interestingly, the alanine-pyruvate cycle was shown indispensable for polyamine utilization. The newly identified dadRAX locus, encoding the regulator, alanine transaminase and racemase respectively, coupled with SpuC, the major putrescine-pyruvate transaminase, were key components to maintain alanine homeostasis. Corresponding mutant strains were severely hampered in polyamine utilization. On the other hand, the alternative gamma-glutamylation pathway for the conversion of putrescine into GABA was also discussed. Subsequently, GabD, GabT and PA5313 were identified for GABA utilization. Growth defect of PA5313 gabT double mutant in GABA suggested the importance of these two transaminases. The succinic-semialdehyde dehydrogenase activity of GabD and its induction by GABA was also demonstrated in vitro. Polyamine utilization in general was proven independent of the PhoPQ two-component system even the expression of which was induced by polyamines. Multiple potent catabolic pathways as depicted in this study could serve pivotal roles in control of intracellular polyamine levels.
Publication Title
Transcriptome analysis of agmatine and putrescine catabolism in Pseudomonas aeruginosa PAO1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.
Publication Title
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
To understand the global view of dysregulated genes and pathwyas in CRYAAN101D lenses, RNA sequencing of 2 & 4 months old CRYAAWT and CRYAAN101D lenses was carried out. Overall design: Determination of differential gene expression between CRYAAWT and CRYAAN101D in 2 & 4 months old lenses
Publication Title
Molecular mechanism of formation of cortical opacity in CRYAAN101D transgenic mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Overall design: Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.
Publication Title
Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 2 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
To investigate the impact of adenosine on gene expression of wild-type PA14.
Publication Title
Interkingdom adenosine signal reduces Pseudomonas aeruginosa pathogenicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 99 Downloadable Samples
- Illumina HiSeq 2500
Description
Characterization of the transcriptome of normal and abnormal embryos. Overall design: Gene expression profiling of every mono and trisomy.
Publication Title
Human blastocysts of normal and abnormal karyotypes display distinct transcriptome profiles.
Sample Metadata Fields
Specimen part, Subject
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