In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. Overall design: DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.
The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.
Specimen part, Subject
View SamplesDefects in mitochondrial metabolism have been increasingly linked with age-onset protein misfolding diseases such as Alzheimers, Parkinsons, and Huntingtons. In response to protein folding stress, compartment-specific unfolded protein responses (UPRs) within the endoplasmic reticulum, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood.
Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.
No sample metadata fields
View SamplesThe host immune response against an infection requires the coordinated action of many diverse cell subsets that dynamically adapt to the pathogen threat. Here we combined WGCNA and DCQ to analyse time-resolved mouse splenic transcriptomes in acute and chronic LCMV infections. This approach allowed to better characterize the dynamic cell events occurring in complex tissues such as the induction of the adaptive T cell response which requires the coordination of monocytes/macrophages and CD8+ T cells. Overall design: mRNA profiles of CD8 T cells and macrophages (in duplicate days 0 and 7 post-infection) from C57BL/6 mice infected with 2x10E2 pfu of LCMV strain Docile, generated by deep sequencing.
Linking Cell Dynamics With Gene Coexpression Networks to Characterize Key Events in Chronic Virus Infections.
No sample metadata fields
View SamplesThe processes and mechanisms of virus infection fate decisions that are the result of a dynamic virus - immune system interaction with either an efficient effector response and virus elimination or an alleviated immune response and chronic infection are poorly understood. Here we characterized the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections by gene coexpression network analysis of time-resolved splenic transcriptomes. We found first, an early attenuation of inflammatory monocyte/macrophage prior to the onset of T cell exhaustion and second, a critical role of the XCL1-XCR1 communication axis during the functional adaptation of the T cell response to the chronic infection state. These findings not only reveal an important feedback mechanism that couples T cell exhaustion with the maintenance of a lower level of effector T cell response but also suggest therapy options to better control virus levels during the chronic infection phase. Overall design: mRNA profiles of spleens (in duplicate, days 0, 3, 5, 6, 7, 9 and 31 post-infection) and macrophages (in triplicate, day 6 post-infection) from C57BL/6 mice infected with 2x10E2 (acute) or 2x10E6 (chronic) pfu of LCMV strain Docile, generated by deep sequencing.
Systems analysis reveals complex biological processes during virus infection fate decisions.
No sample metadata fields
View SamplesTissues of Arabidopsis plants overexpressing artificial microRNAs were compared to wild_type and respective target gene mutants (duplicate arrays)
Highly specific gene silencing by artificial microRNAs in Arabidopsis.
Specimen part
View SamplesThe pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
No sample metadata fields
View SamplesSMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesWild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesSubstantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.
Sample processing obscures cancer-specific alterations in leukemic transcriptomes.
No sample metadata fields
View Samples