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GSE7640
Rattus norvegicus
20 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Physical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection.
Publication Title
Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
Illumina HiSeq 2500
Description
Recurrent mutations in RNA splicing factors SF3B1, U2AF1, and SRSF2 have been reported in hematologic cancers including myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). However, SF3B1 is the only splicing associated gene to be found mutated in CLL and has been shown to induce aberrant splicing. To investigate if any other genomic aberration caused similar transcriptome changes, we clustered RNASeq samples based on an alternative 3' splice site (ss) pattern previously identified in SF3B1-mutant CLL patients. Out of 215 samples, we identified 37 (17%) with alternative 3' ss usage, the majority of which harbored known SF3B1 hotspot mutations. Interestingly, 3 patient samples carried previously unreported in-frame deletions in SF3B1 around K700, the most frequent mutation hotspot. To study the functional effects of these deletions, we used various minigenes demonstrating that recognition of canonical 3' ss and alternative branchsite are required for aberrant splicing, as observed for SF3B1 p.K700E. The common mechanism of action of these deletions and substitutions result in similar sensitivity of primary cells towards splicing inhibitor E7107. Altogether, these data demonstrate that novel SF3B1 in-frame deletion events identified in CLL result in aberrant splicing, a common biomarker in spliceosome-mutant cancers. Overall design: 13 CLL samples, 5 SF3B1 WT, 5 SF3B1 p.K700E, and 3 with in-frame deletions around the K700 position of SF3B1
Publication Title
Novel <i>SF3B1</i> in-frame deletions result in aberrant RNA splicing in CLL patients.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is over-expressed in CLL and is enriched proximal to genes up-regulated or de novo expressed in CLL with known function in disease pathogenesis and progression. These genes, including key members of the BCR signaling pathway, provide rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in pre-clinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 66 Downloadable Samples
Description
Purpose: Here we describe the modulation of a gene expression program involved in cell fate. Methods: We depleted U2AF1 in human induced pluripotent stem cells (hiPSCs) to the level found in differentiated cells using an inducible shRNA system, followed by high-throughput RNAseq, revealing a gene expression program involved in cell fate determination. Results: Approximately 85% of the total raw reads were mapped to the human genome sequence (GRCh37), giving an average of 200 million human reads per sample for total RNA and 15 million human reads per sample for small RNA libraries. Conclusions: Our results show that transcriptional control of gene expression in hiPSCs can be set by the CSF U2AF1, establishing a direct link between transcription and AS during cell fate determination. Overall design: hiPSCs were differentiated into the three germ layers following the described protocol in the study (Gifford et al., 2013).
Publication Title
The core spliceosomal factor U2AF1 controls cell-fate determination via the modulation of transcriptional networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- NextSeq 500
Description
Purpose: To ensure that ABX464 acted specifically on HIV splicing and did not significantly or globally affect the splicing events of human genes, we used an assembly approach of HIV (YU2 strain) putative transcripts and human long non-coding sequences from paired-reads (2x75bp) captured on a NimbleGen SeqCap® EZ Developer Library (Roche/NimbleGen). Methods: Cells were infected with 80 ng of p24/106 cells of the YU-2 strain for 4 to 6 hours and then rinsed with PBS before medium renewal, followed by high-throughput RNAseq from custom SeqCap EZ capture libraries. Each raw dataset of the samples contained between 5 and 30 million paired-end reads (75 bp), with an average of approximately 12 million raw reads per sample. Results: The raw reads were then cleaned and assembled per library to generate contigs, giving an average of 930 contigs per sample for further analyses. Conclusions: Our results show that high-throughput analyses coupled with bioinformatics-specific tools offers a comprehensive and more accurate view of mRNA splicing within a cell. Overall design: We used buffy coats from HIV-negative individuals were obtained from the local blood donation center, then human peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll (Histopaque, Sigma) gradient centrifugation. Cells were infected with 80 ng of p24/106 cells of the YU-2 strain for 4 to 6 hours and then rinsed with PBS before medium renewal.
Publication Title
Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment.
Publication Title
Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 33 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430B Array (moe430b)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Activity-dependent regulation of inhibitory synapse development by Npas4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
we performed a DNA microarray experiment to identify activity-regulated genes that are misregulated in the absence of Npas4.
Publication Title
Activity-dependent regulation of inhibitory synapse development by Npas4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Expression 430B Array (moe430b)
Description
we used DNA microarray analysis to identify genes that are induced by neuronal activity in excitatory neurons at the time when inhibitory synapses are forming and maturing on them.
Publication Title
Activity-dependent regulation of inhibitory synapse development by Npas4.
Sample Metadata Fields
No sample metadata fields
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