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SRP014006
Drosophila melanogaster
8 Downloadable Samples
Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
mRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Publication Title
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
ATP6AP2 is an essential accessory component of the vacuolar H+ ATPase (V-ATPase) and has been associated with intellectual disabilities (ID) and Parkinsonism. ATP6AP2 has been implicated in several signaling pathways, but little is known about its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional ATP6AP2 Drosophila and mouse models in the nervous system. In Drosophila, knockdown of ATP6AP2 induced defective phototaxis and vacuolisation of photoreceptor neurons and pigment cells when deleted in eyes and alteration of short- and long-term memory when deleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered memory for fear. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defect, abnormal number and morphology of synapses, and alteration of axonal transport in fly. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defect leading to axonal and neuronal degeneration in the cortex and the hippocampus. Surprisingly, myelinisation of axons was affected in our mutant mice. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulated genes involved in myelination, action potential, membrane bound vesicles and adult behaviour. In summary, disruption of ATP6AP2 in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. Overall design: 4 samples, 2 wt and 2 Atp6ap2Camk2aCre/0
Publication Title
Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer II
Description
Removal of introns by pre-mRNA splicing is a critical and in some cases rate-limiting step in mammalian gene expression. Deep sequencing of mouse embryonic stem cell RNA revealed many specific internal introns that are significantly more abundant than the other introns within poly(A) selected transcripts; we classify these as “detained” introns (DIs). We identified thousands of DIs flanking both constitutive and alternatively spliced exons in human and mouse cell lines. Drug inhibition of Clk SR-protein kinase activity triggered rapid splicing changes in a specific set of DIs, about half of which showed increased splicing and half increased intron detention, altering the transcript pool of over 300 genes. These data suggest a widespread mechanism by which a nuclear detained pool of mostly processed pre-mRNAs can be rapidly mobilized in response to stress or homeostatic autoregulation. Overall design: v6.5 mouse embryonic stem cells were untreated, treated with the Clk kinase inhibitor KH-CB19, or treated with DMSO as a negative control. Untreated cells were harvested and a single replicate was sequenced using a custom, ligation-based, stranded library preparation protocol. Treated cells were harvested at time 0 and at 2 hours post-treatment, and poly(A)-selected RNA-seq libraries were made from biological duplicates for each treatment/time, barcoded, and sequenced by strand-specific, paired-end sequencing using the Illumina TruSeq kit.
Publication Title
Detained introns are a novel, widespread class of post-transcriptionally spliced introns.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Examination of the genome-wide distribution of 5hmC in osteoarthritic chondrocytes compared to normal chondrocytes in order to elucidate the effect on OA-specific gene expression.
Publication Title
Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
The epigenetic regulator BMI1 is upregulated in many human malignancies and has been implicated in cell migration, but the impact on autochthonous tumor progression is unexplored. Our analyses of human expression data show that BMI1 levels increase with progression in melanoma. We find that BMI1 expression in melanoma cells does not influence cell proliferation or primary tumor growth. In contrast, BMI1 levels are a key determinant of melanoma metastasis, whereby deletion impairs and overexpression enhances dissemination. Remarkably, BMI1’s pro-metastatic effect reflects enhancement of all stages of the metastatic cascade including invasion, migration, extravasation, adhesion and survival. Additionally, downregulation or upregulation of BMI1 induces sensitivity or resistance to BRAF inhibitor. Consistent with these pleiotropic effects, we find that BMI1 promotes widespread gene expression changes that encompass key hallmarks of the melanoma invasive signature, including activation of TGFß, non-canonical Wnt, EMT and EGF/PDGF pathways. Importantly, for both primary and metastatic melanoma samples, this BMI1-induced signature identifies invasive subclasses of human melanoma and predicts poor patient outcome. Our data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance. Overall design: Three replicates of A375 BMI1 or GFP overexpressing cells.
Publication Title
BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differential gene expression in RNA isolated from stably-transfected EBERs-negative versus EBERs-positive HK1 cell lines
Publication Title
Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Regulation of chondrogenic differentiation by DNA demethylation is little understood. The ten-eleven-translocation (TET) proteins oxidize methylated cytosines (5mC) to 5hmC, 5fC and 5caC eventually leading to DNA demethylation. However, 5hmC is stable and can potentially act as an epigenetic mark as well. In this study, we report that global changes in 5hmC mark chondrogenic differentiation.
Publication Title
Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We found that amino acid transporter LHT1 was required for negatively regulating plant defence responses in addition to its physiological role in development and growth. In order to identify which defense pathways were involved in this process, we compared the expression profiles between wild type and lht1 mutant leaves without or with infection by Pseudomonas syringae pv. tomato DC3000 (Pst). In the lht1 mutant, except the changes in nitrogen metabolism-, cellular redox-, and photorespiration-associated gene expressions, the most drastic upregulations were found in the salicylic acid pathway-associated defense genes.
Publication Title
Amino acid homeostasis modulates salicylic acid-associated redox status and defense responses in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples