Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue, a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPAR) in cold-induced browning. Here we aimed to investigate the importance of PPAR in driving transcriptional changes during cold-induced browning in mice. Male wildtype and PPAR/ mice were housed at thermoneutrality (28 C) or cold (5 C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPAR/ mice fasted for 24 h served as positive control for PPAR-dependent gene regulation.Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPAR/ mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPAR genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPAR/ mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPAR/ mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid -oxidation to a similar extent in wildtype and PPAR/ mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPAR/ mice. Finally, pharmacological PPAR activation had a minimal effect on expression of cold-induced genes in murine WAT.Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPAR, indicating that PPAR is dispensable for cold-induced browning.
The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice.
Sex
View SamplesCulturing myotubes from skeletal muscle (SM) biopsies enables investigating transcriptional defects and assaying therapeutic strategies. This study compares the transcriptome of aneurally cultured human SM cells versus that of tissue biopsies.
Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue.
Sex, Specimen part
View SamplesWe identified a subset of hepatocytes with high Telomerase Reverse transcriptase (Tert) that functions as the repopulating stem cells in homeostasis and injury. We performed RNA-Seq to reveal the differences of these cells and the other hepatocytes. Overall design: RNA mRNA profiles of TERT(High) and TERT (Low) hepatocytes from 2-month old mice were generated by deep sequencing, in triplicate, using Illumina platform.
Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury.
Age, Specimen part, Cell line, Subject
View SamplesStatus Epilepticus (SE) is an abnormally prolonged seizure that results from either a failure of mechanisms that terminate seizures or from initiating mechanisms that inherently lead to prolonged seizures.
Induction of Type 2 Iodothyronine Deiodinase After Status Epilepticus Modifies Hippocampal Gene Expression in Male Mice.
Specimen part
View SamplesBackground: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data and validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity, classic dengue fever or dengue hemorrhagic fever (DHF) and compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection
Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome.
Sex, Age
View SamplesIn order to gain insight into the molecular pathogenesis of collagen VI defects we have performed gene expression microarray analysis of dermal fibroblasts. We have compared the transcriptome of fibroblasts, treated or untreated with ascorbic acid, from UCMD patients (n = 6) and aged-matched healthy children (n = 5).
Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators.
Specimen part, Disease, Disease stage, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sex, Disease, Subject, Time
View SamplesBackground: Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training. Results: To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention. Methods: Cold acclimation altered the expression of 756 genes (422 up, 334 down, P<0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P<0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism. Conclusions: Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to cell remodeling rather than metabolic pathways.
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sex, Disease, Subject, Time
View SamplesBackground: Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training. Results: To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention. Methods: Cold acclimation altered the expression of 756 genes (422 up, 334 down, P<0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P<0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism. Conclusions: Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to cell remodeling rather than metabolic pathways.
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sex, Disease, Subject, Time
View SamplesMacrophages 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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