This SuperSeries is composed of the SubSeries listed below.
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Specimen part, Subject, Time
View SamplesMacrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Subject, Time
View SamplesMacrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease. Overall design: Since transcriptional programs are further modulated on several levels including miRNAs we assessed the global spectrum of miRNA expression by miRNA-Seq in macrophages stimulated with IFN?, IL4 or with the combination of TNFa, PGE2 and P3C
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
No sample metadata fields
View SamplesStudy of the tetrapod limb has contributed a great deal to our understanding of developmental pathways and how changes to these pathways affect morphology. Most data on tetrapod limb development is known from amniotes, with far less known about genetic mechanisms of limb development in amphibians. To better understand the mechanisms of limb development in anuran amphibians, we use cyclopamine to inhibit Hedgehog signaling at various stages of limb development in Xenopus. We use transcriptomic analysis following cyclopamine exposure to understand the downstream effects of Hedgehog inhibition on gene expression. We find many aspects of Hedgehog function appear to be conserved with respect to amniotes, including the responses of ptc genes, gremlin, bmp2, and the autoregulatory property of shh. We show that, as was proposed based on experiments in chick, Sonic hedgehog plays two distinct roles in limb development specification of digit number and specification of digit identity. In contrast to these points of conservation, we find that Hedgehog signaling is required for the maintenance of early limb bud outgrowth in Xenopus, a requirement not known for any other tetrapod.
Choosing the right path: enhancement of biologically relevant sets of genes or proteins using pathway structure.
No sample metadata fields
View SamplesIn animals, piRNAs, and their associated Piwi proteins, guard germ cell genomes against mobile genetic elements via an RNAi-like mechanism. In C. elegans, 21U-RNAs comprise the piRNA class and these collaborate with 22G RNAs, via unclear mechanisms, to discriminate self from non-self and selectively and heritably silence the latter. Recent work indicates that 21U-RNAs are post-transcriptional processing products of individual transcription units that produce ~26 nucleotide capped precursors. Yet, nothing is known of how the expression of precursors is controlled or of how primary transcripts give rise to mature small RNAs. We conducted a genome-wide RNAi screen to identify components of the 21U biogenesis machinery. Screening by direct, qPCR-based measurements of mature 21U-RNA levels, we identified 22 genes important for 21U-RNA production, termed TOFUs (Twenty-One-u Fouled Up). We also identified 7 genes that normally repress 21U production. By measuring mature 21U-RNA and precursor levels for the 7 strongest hits from the screen, we have assigned factors to discrete stages of 21U-RNA production. Our work has identified factors separately required for the transcription of 21U precursors, and the processing of these precursors into mature 21U-RNAs, thereby providing an essential resource for studying the biogenesis of this important small RNA class. Overall design: Small RNA and capped small RNA sequencing from total RNA of C. elegans subjected to different RNAi and different C. elegans mutants
A genome-wide RNAi screen identifies factors required for distinct stages of C. elegans piRNA biogenesis.
Age, Subject
View SamplesRapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis, however, remains challenging. Here, we introduce a genomic strategy to functionally characterize such genes, and apply it to LRPPRC (leucine-rich PPR-motif containing), a poorly studied gene that is mutated in Leigh Syndrome, French Canadian type (LSFC).
Mitochondrial and nuclear genomic responses to loss of LRPPRC expression.
Specimen part, Cell line
View SamplesTo seek whether seasonal variation in environmental particulate matter composition affected the global gene response patterns in cultured human cells representing pulmonary and systemic vascular targets.
Comparative gene responses to collected ambient particles in vitro: endothelial responses.
Specimen part
View SamplesAn auxin-binding protein (Abp57) was previously isolated from rice and known to activate plasma membrane proton ATPase. The Abp57 function was characterised by overexpression in the rice and Arabidopsis. The transgene expression was driven by constitutive promoter, CaMV35S. Results from physiological experiments showed that the transgenic lines were tolerant to drought and salinity stress.
Microarray dataset of transgenic rice overexpressing <i>Abp57</i>.
Age, Specimen part
View SamplesIn this study, we determined the expression profiles of Pho4 and Cbf1 targeted genes in phosphate perturbation.
Differential binding of the related transcription factors Pho4 and Cbf1 can tune the sensitivity of promoters to different levels of an induction signal.
No sample metadata fields
View SamplesRNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133 arrays were hybridized with probe from total RNA isolated from blood sampled from 14 umbilical cords and 14 healthy adult humans.
The human reticulocyte transcriptome.
No sample metadata fields
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