Expression microarrays were employed to identify genes induced by phorbol ester and ionomycin stimulation of EL4 cells. EL4 is a murine T cell line. To identify induced genes that were independent of new protein synthesis cells were pre-treated with cycloheximide. This expression study was used in conjunction with histone acetylation ChIP-chip to determine if inducible genes had a specific histone acetylation profile and whether the acetylation profile differed for genes with different kinetics of induction.
Defining the chromatin signature of inducible genes in T cells.
Cell line, Treatment
View SamplesIdentification of imprinted genes expressed in adult CD3+ splenocytes
Hematopoietic reconstitution with androgenetic and gynogenetic stem cells.
Sex, Age, Specimen part
View SamplesTranscriptional profiling of mouse mesenchymal stem/progenitor cells (MSPC) comparing control Ptpn11+/+ MSPC with Ptpn11E76K/+ MSPC. By obtaining 20 million reads of sequence from two pair, we confirmed our cytokine/chemokine array data and quantitative ELISA data from both mouse and patient-derived specimens. CCL3, CCL12, CCL4, and CXCL12 (SDF-1) were aberrantly produced by Ptpn11 mutated MSPCs Overall design: Examination of mouse Ptpn11E76K/+ mesenchymal stem/progenitor cells (MSPC) transcriptional profiling compared to control Ptpn11+/+ MSPC, freshly isolated from Ptpn11E76K/+/Nestin and Ptpn11+/+/Nestin mice. Two replicate per array.
Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment.
Specimen part, Cell line, Subject
View SamplesHeat shock protein 90 (Hsp90) is an emerging therapeutic target in cancer. We report that Hsp90 inhibitors selectively kill DLBCLs that are biologically dependent on the BCL6 transcriptional repressor. We examined the pharmacokinetics, toxicity and efficacy of PUH71, a recently developed purine scaffold Hsp90 inhibitor. PUH71 preferentially accumulated in tumors vs. normal tissues, and unlike the widely used benzoquinone Hsp90 inhibitors, displayed no signs of organ toxicity. PUH71 selectively and potently induced the regression of BCL6-dependent DLBCLs in vivo, through reactivation of key BCL6 target genes and apoptosis.
A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas.
No sample metadata fields
View SamplesThe transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients.
OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells.
Cell line, Time
View SamplesThis study is designed to compare and contrast the temporal and spatial changes in bone formation rates and transcriptional profiles in cortical and cancellous bone cell populations enriched by laser capture microdissection (LCM) in ovariectomized rats administered Scl-Ab by subcutaneous injection for up to 26 consecutive weeks, followed by a recovery period of up to 18 weeks.
Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats.
Sex, Specimen part, Time
View SamplesDietary polyunsaturated fatty acids (PUFA) act as potent natural hypolipidemics and are linked to many health benefits in humans and in animal models. Mice fed long-term a high fat diet, in which medium-chain alpha linoleic acid (ALA) was partially replaced by long-chain docosahexaenoic (DHA) and eicosapentaenoic (EPA) fatty acids, showed reduced accumulation of body fat and prevention of insulin resistance, besides increased mitochondrial beta-oxidation in white adipose tissue and decreased plasma lipids. ALA, EPA and DHA all belong to PUFA of n-3 series. The intestine is a gatekeeper organ for ingested lipids. To examine the potential contribution of the intestine in the beneficial effects of EPA and DHA, this study assessed gene expression changes using whole genome microarray analysis on small intestinal scrapings. The main biological process affected was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR and intestinal fatty acid oxidation measurements ([14C(U)]-palmitate) confirmed significant gene expression differences in a dose-dependent manner. Furthermore, no major changes in the expression of lipid metabolism genes were observed in colonic scrapings. In conclusion, we show that marine n-3 fatty acids regulate small intestinal gene expression patterns. Since this organ contributes significantly to whole organism energy use, this adaptation of the small intestine may contribute to the complex and observed beneficial physiological effects of these natural compounds under conditions that will normally lead to development of obesity and diabetes.
Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet.
No sample metadata fields
View SamplesRationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.
Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.
Sex, Specimen part, Disease, Race
View SamplesA cardinal symptom of Major Depressive Disorder (MDD) is the disruption of circadian patterns. Yet, to date, there is no direct evidence of circadian clock dysregulation in the brains of MDD patients. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain was difficult to characterize. Here we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-hour cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses ('Controls') and 34 MDD patients. Our dataset covered ~12,000 transcripts in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (AnCg), hippocampus (HC), amygdala (AMY), nucleus accumbens (NAcc) and cerebellum (CB). Several hundred transcripts in each region showed 24-hour cyclic patterns in Controls, and >100 transcripts exhibited consistent rhythmicity and phase-synchrony across regions. Among the top ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERB), DBP, BHLHE40(DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in MDD brains, due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This is the first transcriptome-wide analysis of cyclic patterns in the human brain and demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggest novel molecular targets for treatment of mood disorders.
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder.
Subject
View SamplesRNA-seq profiling was conducted on clinically-annotated human post-mortem brain tissues Overall design: We measured the transcriptome in 281 clinically-annotated human post-mortem brain tissues
Post-mortem molecular profiling of three psychiatric disorders.
Sex, Specimen part, Race, Subject
View Samples