We characterized the Drosophila third instar eye disc using single cell RNA-seq and labelled the multiple cell populations. The results identified a novel transcriptional switch in photoreceptors relating to axonal projections. We then performed single cell RNA-seq on rbf (Rb) mutants and compared the results to the WT cell populations. This identified a specific cell population only in the Rb mutant tissue. This cell population has an upregulation of HIF1A and glycolitic genes such as Aldolase and Lactate dehydrogenase. As a result these cells produce lactate and undergo apoptosis. We also show this process to be directly regulated by E2F/Dp. The paper uncovers a novel metabolic aspect of Rb/E2F dependent apoptosis. Overall design: examining WT and Rb mutants third instar eye disc using single cell RNA-seq
Single cell RNA-sequencing identifies a metabolic aspect of apoptosis in Rbf mutant.
Specimen part, Subject
View SamplesAlthough microglial have an essential role in host defense in the brain, the abnormal activation of microglia can lead to devastating outcomes, such as neuroinflammation and neurodegeneration. Emerging evidence increasingly supports that FTY720 (fingolimod), an FDA-approved drug has beneficial effects in the CNSÂ on brain cells and more recently immunosuppressive activities in microglia via modulation of the S1P1 receptor. However, the exact molecular aspects of FTY720 contribution in microglia remain largely unaddressed. To understand the molecular mechanisms underlying the roles of FTY720 in microglia, we performed gene expression profiling in resting, FTY720, LPS and LPS+FTY720 challenged primary microglial cells (PM) isolated from 3-day-old ICR mice and we identified FTY720 target genes and co-regulated modules that were critical in inflammation. By examining RNA-sequencing and binding motif datasets from FTY720 suppressed LPS-induced inflammatory mediators, we also identified unexpected relationships between the inducible transcription factors (TFs), motif strength, and transcription of key inflammatory mediators. Furthermore, we show that FTY720 controls important inflammatory genes targets by modulating STAT1, and IRF8 level at their promoter site. Our unprecedented findings demonstrate that FTY720 could be a useful therapeutic application for neuroinflammatory diseases associated with microglia activation as well as provide a rich resource and framework for future analyses of FTY720 on microglia interaction. Overall design: Murine microglial PM, were treated with FTY720 (1 uM), and with LPS (10 ng/ml) for 4 hrs.
FTY720 (fingolimod) regulates key target genes essential for inflammation in microglial cells as defined by high-resolution mRNA sequencing.
Specimen part, Subject
View SamplesGlobal transcriptome patterns were performed using SHYG-IOE-5h (5h after Estradiol and Mock treatment)
NAC transcription factor speedy hyponastic growth regulates flooding-induced leaf movement in Arabidopsis.
Specimen part, Treatment
View SamplesInrauterine growth restriction was induced by chronic hyper insulinemia in pregnant rats and differential gene expression was studied using affymetrix rat genome RAE230A.Data was analysed using SAM.
Adult hypertension in intrauterine growth-restricted offspring of hyperinsulinemic rats: evidence of subtle renal damage.
No sample metadata fields
View SamplesImpressive studies have been well documented that Enhancer of zeste homolog 2 (EZH2) could have a role in inflammation as well as a wide range of malignancies; however, the underlying mechanisms remain largely unaddressed. Microglial activation is a key process in the production and release of numerous pro-inflammatory mediators that plays an important role in central nervous system (CNS) inflammation and neurodegeneration. Therefore, our aim was to investigate whether inhibition of EZH2 with selective small molecule inhibitors EPZ-6438 protects against neonatal microglia activation. First, we find that BV-2 microglia, LPS can rapidly increase EZH2 mRNA level and subsequently we performed gene expression profiles and networks in resting, EPZ-6438, LPS and LPS+EPZ-6438 challenged BV-2 microglia by transcriptome RNA sequencing and bioinformatic analyses. By examining RNA sequencing we identified EPZ-6438 target genes and co-regulated modules that were critical in inflammation. We also identified unexpected relationships between the inducible transcription factors (TFs), motif strength, and the transcription of key inflammatory mediators. Furthermore, we showed that EPZ-6438 controls important inflammatory genes targets by modulating interferon regulatory factor (IRF) 1, IRF8, Signal transducer and activator of transcription (STAT) 1 levels at their promoter site. Our unprecedented findings demonstrate that pharmacological interventions built upon EZH2 inhibition by EPZ-6438 could be a useful therapeutic application in neuroinflammatory diseases associated with microglia activation. Overall design: to investigate whether inhibition of EZH2 with selective small molecule inhibitors EPZ-6438 protects against neonatal microglia activation
Selective inhibition of EZH2 by a small molecule inhibitor regulates microglial gene expression essential for inflammation.
Specimen part, Treatment, Subject
View SamplesIn this study we plan to compare the profiles of control sample (C) with the disease (FSGS) samples to identify differentially expressed genes. We hope to identify genes that are specifically activated in response to treatment with FSGS plasma. Overall design: Upregulated genes on incubating with plasma from recurrent FSGS plamsa sample in cultured human podocytes cells were probed
Development of a novel cell-based assay to diagnose recurrent focal segmental glomerulosclerosis patients.
Specimen part, Disease, Subject
View SamplesPersistent microglia activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylases JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 on a transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4, LPS and LPS+GSK-J4 challenged primary microglial (PM) and BV-2 microglial cells. Among the annotated genes, transcriptional sequencing of microglia that were treated with GSKJ4 revealed a selective effect on LPS induced gene expression in which the induction of cytokines/chemokines, interferon-stimulated genes, and prominent (transcription factors) TFs as well as previously unidentified genes that are important in inflammation was suppressed. Furthermore, we show that GSK-J4 controls important inflammatory genes targets by modulating STAT1, IRF7, and H3K27me3 level at their promoter site. These unprecedented results demonstrate the histone demethylases inhibitor GSK-J4 could have therapeutic applications for neuroinflammatory diseases. Overall design: Examination of the effects LPS on GSKJ4-treated PM microglial cells, were generated by deep sequencing on an Illumina HiSeq 2000 (101 cycles PE lane).
RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor.
Specimen part, Treatment, Subject
View SamplesALL is the most common form of childhood cancer with >80% cured with contemporary treatment protocols. Accurate risk stratification in childhood ALL is essential to avoid under- and over-treatment. Currently, we use presenting clinical, biological features, and minimal residual disease (MRD) quantitation to risk stratify patients. Although whole genome gene expression profiling (GEP) can accurately classify patients with ALL into various WHO 2008 defined subgroups, its value in predicting relapse remained to be defined. We hypothesized that global time-series GEPs of bone marrow (BM) samples at diagnosis and specific points during initial remission-induction therapy can measure the success of cytoreduction and be used for relapse prediction.
Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time-series gene expression profiling.
Specimen part, Disease, Subject, Time
View SamplesAerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae grown with six different nitrogen sources were subjected to transcriptome analysis. The use of chemostats enabled an analysis of nitrogen-source-dependent transcriptional regulation at a fixed specific growth rate. A selection of preferred (ammonium and asparagine) and non-preferred (leucine, phenylalanine, methionine and proline) nitrogen sources was investigated. For each nitrogen source, distinct sets of genes were induced or repressed relative to the other five nitrogen sources. A total number of 131 of such signature transcripts were identified in this study. In addition to signature transcripts, genes were identified that showed a transcriptional co-response to two or more of the six nitrogen sources. For example, 33 genes were transcriptionally up-regulated in leucine-, phenylalanine- and methionine-grown cultures, which was partly attributed to the involvement of common enzymes in the dissimilation of these amino acids. In addition to specific transcriptional responses elicited by individual nitrogen sources, their impact on global regulatory mechanisms such as nitrogen catabolite repression (NCR) could be monitored. NCR-sensitive gene expression in the chemostat cultures showed that, ammonia and asparagine were rich nitrogen sources. By this criterion, leucine, proline and methionine were poor nitrogen sources and phenylalanine showed an intermediate NCR response.
Transcriptional responses of Saccharomyces cerevisiae to preferred and nonpreferred nitrogen sources in glucose-limited chemostat cultures.
No sample metadata fields
View SamplesUsing RNA-seq, we report that jumonji H3K27 demethylase inhibitor, GSK-J4, exerts potent anti-inflammatory effects on LPS-stimulated BV-2 microglial cells. Overall design: Examination of effects of LPS-stimulated BV2 cells with or without GSKJ4 treatment, were generated by deep sequencing on an Illumina HiSeq 2000(101 cycles PE lane).
Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia.
Specimen part, Cell line, Treatment, Subject
View Samples