One of the hallmarks in hypertension is a pressure-induced change in endothelial cell phenotype. A cytoskeletal protein zyxin, which was seen to translocate from focal adhesion contacts to the nucleus in response to the increased wall tensionis, mediates the tension-induced endothelial signaling.
Zyxin mediation of stretch-induced gene expression in human endothelial cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress.
Specimen part
View SamplesParkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (Discovery set) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (Validation set). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.
Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.
Specimen part, Disease
View SamplesThere is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of bystander T cell activation occur during immune responses is hotly debated.
Human CD4+ memory T cells are preferential targets for bystander activation and apoptosis.
No sample metadata fields
View SamplesRNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing Overall design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.
Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150.
Cell line, Subject
View SamplesThe classical concept of bone marrow-derived mesenchymal stem cells (BM-MSC), intended as a uniform, broad potent population, is progressively being substituted by the idea that the bone marrow harbors heterogeneous populations of non-hematopoietic stem cells. This in vivo heterogeneity is also amplified by the different experimental strategies used to isolate/culture them. Among the exogenous factors described to affect MSC in vitro growth, basic-fibroblast growth factor (bFGF) is one of the most common growth factors used to expand stem cells. Moreover, it has been reported that its signaling is associated with the mainteinance of stemness of a variety of stem cells, included MSC. Using an ectopic model of bone regeneration, we have previously described that the implantation of cells with different commitment levels, differentially influences the capacity to recruit host cells, activating endogenous regenerative mechanisms. Due to its properties, we here demonstrate that the addition of bFGF to primary BM cultures, leads to the selection of specific subpopulations able to induce a different host regenerative response, when in vivo implanted in association with suitable ceramic scaffolds. Moreover, taking advantage of a multiparametric and comparative genomic and proteomic approach, it has been evaluated how different culture conditions combine to bring about appreciable changes in the secretome of the cells, that consequently influence their in vivo regenerative behaviour. The full comprehension of the regulatory mechanisms that rule the host response depending on the type and differentiative stage of the transplanted cells could help us to develop novel clinical strategies where host cells could directly contribute to regenerate the appropriate tissue.
The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model.
Specimen part, Disease
View SamplesWhole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders.
Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesHuntington''s Disease (HD) is a fatal neurodegenerative disorder caused by an extended polyglutamine repeat in the N-terminus of the huntingtin (Htt) protein. Reactive microglia and elevated cytokine levels are observed in the brains of HD patients, but the extent to which neuroinflammation results from extrinsic or cell-autonomous mechanisms is unknown. Furthermore, the impact of microglia activation on the pathogenesis of HD remains to be established. Using genome-wide approaches, we show that expression of mutant Htt in microglia promotes cell-autonomous pro-inflammatory transcriptional activation within microglia by increasing the expression and transcriptional activities of the myeloid lineage-determining factors PU.1 and C/EBPs. Elevated levels of PU.1 and its target genes are observed in the brains of mouse models and HD individuals. Moreover, mutant Htt expressing microglia exhibit an increased capacity to induce neuronal death ex vivo and in vivo in the presence of sterile inflammation. These findings suggest that expression of mutant Htt in microglia may contribute to neuronal pathology in Huntingtin disease. Overall design: RNA-Seq and ChIP-Seq for PU.1, C/EBP, and H3K4me2 in BV2 cells and RNA-Seq in primary microglia and macrophages
Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders.
Age, Specimen part
View SamplesThe aim was to analyze the transcriptome of different types of preneoplastic colorectal lesions in comparison with that of the corresponding normal mucosa.
Preinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid).
Specimen part
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