Macrophages polarize to divergent functional phenotypes depending on their microenvironment in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified 7 major (novel and known) regulatory modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included: inflammatory variant of the aspartate-arginosuccinate shunt; TCA cycle break at Idh expression accompanied by citrate accumulation and production of itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine in polarization, providing nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation results in significant M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization. Overall design: Bone-marrow derived macrophages were generated from C57BL/6 mice were plated at ~100k cells per well in 96-well plate and stimulated with either Il4 or combination of LPS&IFNg or left unstimulated for 24 h mRNA was derived from lysates using Invitrogen oligo-dT beads
Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages.
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H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.
Specimen part, Cell line
View SamplesCellular senescence is a tumor-suppressive program that involves chromatin reorganization and specific changes in gene expression that trigger an irreversible cell-cycle arrest. We have examined the effect of suppressing the histone demethylases Jarid1a and Jarid1b on the senescence-associated gene expression signatures.
H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.
Specimen part, Cell line
View SamplesInsulin resistance is a sine qua non of Type 2 diabetes (T2D) and a frequent complication of multiple clinical conditions, including obesity, aging, and steroid use, among others. How such a panoply of insults can result in a common phenotype is incompletely understood. Furthermore, very little is known about the transcriptional and epigenetic basis of this disorder, despite evidence that such pathways are likely to play a fundamental role. Here, we compare cell autonomous models of insulin resistance induced by the cytokine tumor necrosis factor-a (TNF) or by the steroid dexamethasone (Dex) to construct detailed transcriptional profiles associated with cellular insulin resistance.
Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis.
Specimen part, Cell line, Treatment, Time
View SamplesG9a is an H3K9m2 methyltransferase, which is critical in controlling gene suppression and DNA methylation. We used microarray analysis to identify the target genes that are regulated by G9a in MDA-MB231 cells, in which E-cadherin is silenced.
G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer.
Specimen part, Cell line, Treatment
View SamplesBesides the established selection criteria based on embryo morphology and blastomere number, new parameters for embryo viability are needed to improve the clinical outcome of in vitro fertilization (IVF) and more particular of elective single embryo transfer (eSET). The aim of the study was to analyse genome-wide whether the embryo viability was reflected by the expression of genes in the oocyte surrounding cumulus cells. Early cleavage (EC) was chosen as a parameter for embryo viability.
Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis.
No sample metadata fields
View SamplesGene expression changes in the heart of MCH3-KO mouse (HDAC3 f/f, Muscle Creatine Kinase-Cre) versus control WT mouse (HDAC3 f/f).
Diet-induced lethality due to deletion of the Hdac3 gene in heart and skeletal muscle.
Specimen part
View SamplesGrowth in dense stands induces shade avoidance responses. Early responses to neighbors seem to be assoctaed with touch, not light signalling.
Plant neighbor detection through touching leaf tips precedes phytochrome signals.
Specimen part
View SamplesIn dense stands,the earliest neighbor response is induced by touching,leading to shade avoidance. During light competion the R:FR distribution is not homogenous, leading to local differences in light quality (R:FR) within the same leaf. Hyponasty is induced by FR-signaling in the lamina tip, which then induces local cell growth in the petiole base. Likewise, local touching of the leaf tip induces a similar phenoype.
Neighbor detection at the leaf tip adaptively regulates upward leaf movement through spatial auxin dynamics.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-infected brain: novel analysis of retrospective cases.
Sex, Age, Specimen part
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