To identify novel Nurr1 target genes we have used microarrays strategies in rat midbrain primary cultures, enriched in dopaminergic neurons, by the action of basic fibroblast growth factor (bFGF, 20ng/ml) and Sonic hedgedog (SHH), following upregulation of Nurr1 expression by depolarization.To this aim we have treated the cultures after 9 days in vitro for 2h with high KCl and collected 30 min or 2 h after the end of depolarization (2h + 30 min or 2h + 2h). With this experimental protocol we have identify a putative Nurr1 regulator and Nurr1 target
Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro.
Specimen part
View SamplesTo determine a gene/molecular fingerprint of multiple myeloma (MM) endothelial cells (MMECs), also identifying some of the vascular mechanisms that govern the malignant progression from quiescent monoclonal gammopathy of undetermined significance (MGUS). A comparative gene expression profiling (GEP) was carried out on patient-derived MMECs and MGUS endothelial cells (MGECs) using the Affymetrix U133A Arrays. Expression of selective vascular markers were also validated by RT-PCR and immunoblotting analysis in primary cultures of ECs isolated from total bone marrow (BM)-mononuclear cells. Twenty-two genes were found differently expressed in MMECs compared to MGECs (with 14 down-regulated and 8 up-regulated), thus proving that molecular differences were maintained in vitro. Specific pathways analysis revealed transcriptional and protein expression changes for key regulators of extracellular matrix formation and bone remodeling, cell-adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Specifically, we focused on six of these genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3 and SEPW1), which were not previously functionally correlated to the overangiogenic phenotype of MMECs and disease activity. These data identified distinct EC gene expression profiles and some vascular phenotypes that could influence the remodeling of the BM-microenvironment in patients with active MM. A better understanding of the linkage between genetic and epigenetic events in MM tumor/ECs may contribute to the molecular classification of the disease, thereby identifying selective targets of more effective anti-vessel/stroma therapeutic strategies.
Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
Sex
View SamplesAnalysis of gene expression profiles in Induced T-to-Natural Killer (ITNK), compared to DN3 parental T cells and IL-2-expanded NK cells (LAK). The hypothesis tested in the present study was that gene expression profiles of ITNK that were derived from DN3 T cells after deletion of Bcl11b were more similar to LAK, rather than DN3 T cells. Results provide important information of the ITNKs, such as canditate genes regulated by Bcl11b, up-regulated important genes expressed in NK cells, and down-regulated T cell genes.
Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion.
Specimen part
View SamplesDengue virus (DENV) infection is one of the most serious public health problems worldwide. A recent dengue outbreak in Paraguay (2007-2009) presented unusual manifestations such as hepatitis, encephalitis, pulmonary as well as cardiac disorders associated with 50% of deaths caused by dengue in the country. Despite the knowledge on inflammatory responses observed during the course of disease, the role of innate immune cells in the control of virus replication influencing clinical outcome is poorly defined. Using two clinical isolates of the virus, a non-fatal case of classical DF (DENV3/290) and a fatal case of DF with visceral complications (DENV3/5532), we sought to determine the profile of dengue infection in human dendritic cell, a major innate immune cell population. Compared to classical DENV3/290, the strain DENV3/5532 displayed higher replicative ability in mdDCs. In addition, DENV3/5532 was found to induce elevated production of pro-inflammatory cytokines associated with higher rates of programmed cell death. The observed phenotype was due to viral replication in mdDCs and TNF appeared to display a protective effect on virus-induced mdDCs apoptosis. These results suggest that the fatal case DENV3/5532 isolate modulates dendritic cell survival as well as inflammatory mediators synthesis.
Dengue virus type 3 isolated from a fatal case with visceral complications induces enhanced proinflammatory responses and apoptosis of human dendritic cells.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Specimen part
View SamplesAnalysis of early changes in the R-H model of carcinogenesis in order to investigate the relationship between oval cell proliferation and preneoplastic foci
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Specimen part
View SamplesAnalysis of early changes in the R-H model of carcinogenesis in order to investigate the relationship between oval cell proliferation and preneoplastic foci
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Specimen part
View SamplesHere we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null) and EZH2+/+ (WT) human ESC
Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Specimen part, Subject
View SamplesOur study demonstrates that neutrophils infiltrate early-stage PTEN-deficient uterine tumors and oppose tumor growth and malignant progression by inducing detachment and ultimately promoting cell death of tumor cells. This RNA-seq study examined the expression profiles of these uterine epithelial tumor cells in the presence versus absence of neutrophil infiltration. Overall design: Tumor cells from 4-week-old tumor-bearing neutrophil-sufficient versus -deficient mice were isolated by fluorescence activated cell sorting, RNA was isolated, and expression profiles were analyzed by deep sequencing.
Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.
Age, Specimen part, Subject
View SamplesThe homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.
Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.
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