The knowledge of an expression network signature in end-stage heart failure (HF) diseased hearts may offer important insights into the complex pathogenesis of advanced cardiac failure, as well as it may provide potential targets for therapeutic intervention. In this study, the NGS sequencing of RNA (RNA-Seq) method was employed to obtain the whole transcriptome of cardiac tissues from transplant recipients with advanced stage of HF. The analysis of RNA-Seq data presents novel challenges and many methods have been developed for the purpose of mapping reads to genomic features and quantifying gene expression. The main goal of this work was to identify, characterize and catalogue all the transcripts expressed within cardiac tissue and to quantify the differential expression of transcripts in both physio- and pathological conditions through whole transcriptome analyses. Expression levels, differential splicing, allele-specific expression, RNA editing and fusion transcripts constitute important information when comparing samples for disease related studies. Analysis methods for RNA-Seq data are continuing to evolve. Thus, in order to find the best solution for filter generated list of differentially expressed genes, an informatic approach of NOISeq BIO method has been applied in this RNA-Seq analysis. Most of the genes obtained by filtering differentially expressed gene list, have been experimentally validated by Real time RT-PCR. Noteworthy, these findings provide valuable resources for further studies of the molecular mechanisms involved in heart ischemic response thus leading to potential novel biomarkers and targets for therapeutic intervention in the onset and progression of cardiomyopathies. Overall design: Heart biopsies from candidates for solid organ transplantation were collected and their RNA samples were used for high-throughput sequencing purposes. Libraries were sequenced on the Illumina HiSeq2000 NGS platform.
Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing.
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View SamplesGenome-wide assessment of gene expression in primary acute lymphoblastic leukemia cells was performed to identify genomic determinants of MTXs antileukemic effects. Reduction of circulating leukemia cells after in vivo methotrexate treatment served as a measure MTX's antileukemic effects.
In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile.
No sample metadata fields
View SamplesBackground: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sex
View SamplesFull title: Expression data from human primary subcutaneous preadipocytes treated with glucocorticoids prior to the initiation of differentiation.
Insulin sensitization of human preadipocytes through glucocorticoid hormone induction of forkhead transcription factors.
Specimen part
View SamplesTo identify targets of PDGFRb signaling and potentially new markers for pericyte activation, we used microarray analysis to compare gene expression in control and mutant pericytes expressing a constitutively active PDGFRb.
PDGFRβ signaling regulates mural cell plasticity and inhibits fat development.
Specimen part
View SamplesPDGF and FGF treatment in E13.5 MEPMs. 4 hr PDGF treated MEPMs (3 replicates), 4 hr FGF treated MEPMs (3 replicates), 1 hr PDGF + PD325901 treated MEPMs (2 replicates), 4 hr PDGF + PD325901 treated MEPMs (2 replicates), 1 hr FGF + PD325901 treated MEPMs (2 replicates), 4 hr FGF + PD325901 treated MEPMs (2 replicates), 1 hr PDGF + LY294002 treated MEPMs (2 replicates), 4 hr PDGF + LY294002 treated MEPMs (2 replicates), 1 hr FGF + LY294002 treated MEPMs (2 replicates), 4 hr FGF + LY294002 treated MEPMs (2 replicates) Overall design: 4 hr PDGF treated MEPMs (3 replicates), 4 hr FGF treated MEPMs (3 replicates), 1 hr PDGF + PD325901 treated MEPMs (2 replicates), 4 hr PDGF + PD325901 treated MEPMs (2 replicates), 1 hr FGF + PD325901 treated MEPMs (2 replicates), 4 hr FGF + PD325901 treated MEPMs (2 replicates), 1 hr PDGF + LY294002 treated MEPMs (2 replicates), 4 hr PDGF + LY294002 treated MEPMs (2 replicates), 1 hr FGF + LY294002 treated MEPMs (2 replicates), 4 hr FGF + LY294002 treated MEPMs (2 replicates)
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways.
No sample metadata fields
View SamplesReceptor tyrosine kinase signaling is critical for mammalian craniofacial development, but the key downstream transcriptional effectors remain unknown. We demonstrate that SRF is induced by both PDGF and FGF signaling in mouse embryonic palatal mesenchyme cells, and Srf neural crest conditional mutants exhibit facial clefting accompanied by proliferation and migration defects. Srf and Pdgfra mutants interact genetically in craniofacial development, but Srf and Fgfr1 mutants do not. This signal specificity is recapitulated at the level of cofactor activation: while both PDGF and FGF target gene promoters show enriched genome-wide overlap with SRF ChIP-seq peaks, PDGF selectively activates a network of MRTF-dependent cytoskeletal genes. Collectively, our results identify a novel role for SRF in proliferation and migration during craniofacial development and delineate a mechanism of receptor tyrosine kinase specificity mediated through differential cofactor usage, leading to a unique PDGF-responsive SRF-driven transcriptional program in the midface. Overall design: Serum Starved MEPMs (4 replicates), 1 hr PDGF treated MEPMs (4 replicates), 1 hr FGF treated MEPMs (3 replicates)
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways.
No sample metadata fields
View SamplesNovel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006.
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
Sex, Age, Disease stage
View SamplesHalf of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated, amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. Overall design: Vehicle vs. ReACp53 treatment in 4 different samples: 2 cell lines (MCF7 w/ WT p53 as negative control and OVCAR3 w/ R248Q p53) and 2 clinical specimens (primary cells from patient #8 w/ WT p53 as negative control and primary cells from patient #1 w/ R248Q p53)
A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas.
No sample metadata fields
View SamplesFull title: Genome-wide expression profiles of primary human small airway epithelial cells (SAECs) infected with different adenovirus mutants.
Heterochromatin silencing of p53 target genes by a small viral protein.
Specimen part
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