The LIM-only protein FHL2 is expressed in SMCs and inhibits SMC-rich lesion formation. However, the underlying mechanism behind FHL2's action in SMCs has been only partially resolved. To further elucidate the role of FHL2 in SMCs we compared the transcriptome of cultured SMCs derived from wild-type (WT) and FHL2-knockout (KO) mice.
LIM-only protein FHL2 is a positive regulator of liver X receptors in smooth muscle cells involved in lipid homeostasis.
Specimen part
View SamplesActivation of macrophages by inflammatory stimuli leads to reprogramming of mitochondrial metabolism to support the production of pro-inflammatory cytokines. Hallmarks of this metabolic rewiring are downregulation of a-ketoglutarate formation via isocitrate dehydrogenase (IDH) and accumulation of glutamine-derived succinate, which enhances the inflammatory response via the activity of succinate dehydrogenase (SDH). Here, we identify the nuclear receptor Nur77 (Nr4a1) as a key regulator of the pro-inflammatory metabolic switch in macrophages. Nur77-deficient macrophages fail to downregulate IDH expression and accumulate higher levels of succinate and other downstream TCA cycle metabolites in response to an inflammatory stimulus. Consequently, these macrophages produce more nitric oxide and pro-inflammatory cytokines in an SDH-dependent manner. In vivo, bone marrow Nur77 deficiency exacerbates atherosclerosis development and leads to increased systemic succinate levels. In conclusion, Nur77 supports an anti-inflammatory metabolic state in macrophages that protects against chronic inflammatory diseases such as atherosclerosis. Overall design: Gene expression profiling by RNA-seq was performed in triplicate in RAW264.7 mouse macrophage stable cell lines with doxycycline-inducible overexpression of HA-tagged NUR77 or GFP as control.
Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism.
Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Sex, Age
View SamplesAging is associated with major nuclear changes affecting genomic integrity and gene expression. Here we compare the gene expression profiles in the neocortex of young (5 months old) and old (30 months old) B6xC3 F1 mice.
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Sex, Age
View SamplesA study evaluating the effect of stress resistance selection of Drosophila melanogaster.
Gene expression profile analysis of Drosophila melanogaster selected for resistance to environmental stressors.
No sample metadata fields
View SamplesTranscriptional variation, also called expression level polymorphism (ELP), contributes to intra-specific phenotypic variation in many organisms. Differentially expressed transcripts are typically enriched for stress-related genes, suggesting that differences in response to the environment are a particularly common point of divergence among gentoypes. Analysis of ELPs also has been suggested as a way to assess unintended consequences of transgene introduction; however, it is important that interpretation of transcriptional changes be performed within the context of potential fitness effects. In these studies we sought to examine differential gene expression in response to salinity for two widely used Arabidopsis thaliana ecotypes, Wassilewskija (Ws) and Columbia (Col), and a single gene mutation (glabrous, gl1-1) in the Col background (Col(gl)), in relation to genetic, phenotypic, and fitness differences.
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes.
Age, Specimen part
View SamplesMannitol is a putative osmoprotectant contributing to salt tolerance in several species. Arabidopsis plants transformed with the mannose-6-phosphate reductase (M6PR) gene from celery were dramatically more salt tolerant (at 100mM NaCl) as exhibited by reduced salt injury, less inhibition of vegetative growth, and increased seed production relative to the wild type (WT). When treated with 200mM NaCl, transformants produced no seeds, but did bolt, and exhibited less chlorosis/necrosis and greater survival and dry weights than the WT. Without salt there were no M6PR effects on growth or phenotype, but expression levels of 2272 genes were altered. Many fewer differences (1039) were observed between M6PR and WT plants in the presence of salt, suggesting that M6PR pre-conditioned the plants to stress. Previous work suggested that mannitol is an osmoprotectant, but mannitol levels are invariably quite low, perhaps inadequate for osmoprotectant effects. In this study, transcriptome analysis reveals that the M6PR transgene activated the downstream abscisic acid (ABA) pathway by up-regulation of ABA receptor genes (PYL4, PYL5, and PYL6) and down-regulation of protein phosphatase 2C genes (ABI1 and ABI2). In the M6PR transgenic lines there were also increases in transcripts related to redox and cell wall-strengthening pathways. These data indicate that mannitol-enhanced stress tolerance is due at least in part to increased expression of a variety of stress-inducible genes.
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes.
Age, Specimen part
View SamplesEngineered abiotic stress resistance is an important target for increasing agricultural productivity.There are concerns, however, regarding possible ecological impacts of transgenic crops. In contrast to the first wave of transgenic crops, many abiotic stress resistance genes can initiate
Comparison of salt stress resistance genes in transgenic Arabidopsis thaliana indicates that extent of transcriptomic change may not predict secondary phenotypic or fitness effects.
Age, Specimen part, Treatment
View SamplesWe used microarrays to investigate the transcriptome of 6 days old male flies exposed to either 15 or 25 C development at either constant or fluctuating temperatures. Further, we investigated gene expression at benign (20C) and high (35C) temperatures
Thermal fluctuations affect the transcriptome through mechanisms independent of average temperature.
Sex
View Samplesgene expression was measured in control and heat resistance selected adult female flies before and at 8 time points after heat stress for 1h @ 36 degrees
Full genome gene expression analysis of the heat stress response in Drosophila melanogaster.
No sample metadata fields
View Samples