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GSE85017
Homo sapiens
38 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Alternative splicing (AS) is a post-transcriptional gene regulatory mechanism that contributes to proteome diversity. Aberrant splicing mechanisms (mutations, polymorphisms, insertion/deletion etc.) contribute to various cancers and muscle related conditions such as Duchenne muscular dystrophy. However, dysregulation of AS in Cancer Cachexia (CC) patients remains unexplored. Our objectives were (i) to profile alternatively spliced genes (ASGs) on a genome-wide scale, and (ii) to identify DE alternatively spliced genes (DASGs) associated with CC. Rectus abdominis muscle biopsies obtained from cancer patients were stratified into cachectic cases (n=21, classified based on International consensus diagnostic framework for CC) and non-cachectic controls (n=19, weight stable cancer patients). Human Transcriptome array 2.0 was used for profiling ASGs using the total RNA isolated from muscle biopsies. Representative DASG signatures were validated using semi-quantitative RT-PCR. We identified 8960 ASGs, of which 922 DASGs (772 up-regulated, 150 down-regulated) were identified at > 1.4 fold-change and p < 0.05. Representative DASGs when validated by semi-quantitative RT-PCR also showed similar trends, confirming the primary findings from the genome-wide arrays. Identified DASGs were associated with myogenesis, adipogenesis, protein ubiquitination and inflammation. Up to 10% of the DASGs exhibited cassette exon (exon included or skipped) as a predominant form of AS event. We also observed other forms of AS events such as intron retention, alternate promoters. Overall, we have, for the first time conducted global profiling of muscle tissue to identify DASGs associated with CC. The mechanistic roles of the identified DASGs in CC pathophysiology using model systems is warranted, as well as replication of findings in independent cohorts.
Publication Title
Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The H2A variant H2AZ is essential for embryonic development and for proper execution of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions in H2AZ are likely key for its functional specialization, but we know little about how these differences contribute to chromatin regulation. Here, we show that the extended acidic patch, specifically the three divergent residues in the C-terminal docking domain, is necessary for lineage commitment during ESC differentiation and proper execution of gene expression programs during ESC differentiation. Surprisingly, disruption of the acidic patch domain has a distinct consequence on cellular specification compared to H2AZ depletion. This is consistent with differences in gene expression profiles of H2AZ –depleted and acidic patch (AP) mutant ESCs during early lineage commitment. Interestingly, the distinct consequence of AP mutant expression on gene regulation is coincidence with an altered destabilized chromatin state and high chromatin mobility dependent on active transcription. Collectively, our data shows that the divergent residues within the acidic patch domain are key structural determinants of H2AZ function and links chromatin structure and dynamics with gene regulation and cell fate specification. Overall design: H2AZ extended acidic patch was mutated, or H2AZ was KD in mouse embryonic stem cells and RNA-Seq analysis was performed on the resulting cultures. Characterization of H2AZ-WT and -AP3-mutant binding specificities were performed by ChIP-Seq.
Publication Title
H2A.Z acidic patch couples chromatin dynamics to regulation of gene expression programs during ESC differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Illumina Genome Analyzer
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina Genome Analyzer, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Estrogen receptor (ER) is a key regulator of breast growth and breast cancer development. However, the role of ER in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ER with estrogen induced transcript and metabolic profiling, we demonstrate that ER reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ER target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ER promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ER for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ER target CHPT1 in breast cancer supports its potential as a therapeutic target.
Publication Title
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 235 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Isoniazid induced varying degrees of hepatic steatosis in an inbred strain Mouse Diversity Panel (MDP) study. RNA was isolated from all animals for analysis of gene expression changes in the liver. The objective of this study was to identify gene expression changes that drive isoniazid-induced steatosis.
Publication Title
A systems biology approach utilizing a mouse diversity panel identifies genetic differences influencing isoniazid-induced microvesicular steatosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Study of HP1 Knock Down on gene expression and splicing regulation in Human HeLa cells
Publication Title
Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 83 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The whole blood was collected pre-treatment from rheumatoid arthritis patients starting the anti_TNF therapy. All patients were nave to anti_TNFs. The disease activity was measured using the DAS28 score at the pre-treatment visit1 (DAS28_v1) and 14 weeks after treatment visit3 (DAS28_v3). The response to the therapy was evaluated using the EULAR [European League Against Rheumatism] definition of the response. The objective of the data analysis was to identify gene expression coorelating with response as well as to identify genes that differentiate responders versus non-responders pre-treatment. The results of this investigation identified 8 trainscripts that predict responders vs. non-responders with 89% accuracy.
Publication Title
Convergent Random Forest predictor: methodology for predicting drug response from genome-scale data applied to anti-TNF response.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray analysis was used to compare the gene expression profiles of Deaf-1-transduced mouse mammary epithelial cells (MECs) relative to Deaf-1-deficient MECs.
Publication Title
Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
The heat shock response (HSR) is a mechanism to cope with proteotoxic stress by inducing the expression of molecular chaperones and other heat shock response genes. The HSR is evolutionarily well conserved and has been widely studied in bacteria, cell lines and lower eukaryotic model organisms. However, mechanistic insights into the HSR in higher eukaryotes, in particular in mammals, are limited. We have developed an in vivo heat shock protocol to analyze the HSR in mice and dissected heat shock factor 1 (HSF1)-dependent and -independent pathways. Whilst the induction of proteostasis-related genes was dependent on HSF1, the regulation of circadian function related genes, indicating that the circadian clock oscillators have been reset, was independent of its presence. Furthermore, we demonstrate that the in vivo HSR is impaired in mouse models of Huntington's disease but we were unable to corroborate the general repression of transcription after a heat shock found in lower eukaryotes. Overall design: RNA-Seq was performed on mRNA isolated from quadriceps femoris muscle of 24 mice. These mice were of wild type, R6/2, and Hsf1-/- genotypes. Two mice of each genotype were tested in four conditions: (1) heat shock, (2) control heat shock, (3) HSP90 inhibition (NVP-HSP990), and (4) HSP90 inhibition vehicle.
Publication Title
HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Phosphorylation of histone H3 at Serine 10 emerges as a mechanism increasing chromatin accessibility of the transcription factor NF-kB for a particular set of immune genes. Here we report that a bacterial pathogen uses this strategy to shape the transcriptional response of infected host cells. We identify the Shigella flexneri type III protein effector OspF as a Dual Specific Phosphatase. OspF dephosphorylates MAP kinases within the nucleus impairing histone H3 phosphorylation at Serine 10 in a gene-specific manner. Therefore, OspF reprograms the transcriptional response for inactivation of a subset of NF-kB responsive genes. This regulation leads to repression of polymorphonuclear leukocytes recruitment in infected tissues. Thus, pathogens have evolved the ability to precisely modulate host cell epigenetic information as a strategy to repress innate immunity.
Publication Title
An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.
Sample Metadata Fields
No sample metadata fields
View Samples