The goal of this study is to determine the effects of adipose-specific Glut4 overexpression or knockout on changes in adipose tissue global gene expression
A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
Sex, Age
View SamplesObesity is an epidemic health problem worldwide that impacts the risk and prognosis of many diseases. However, not all obese patients have the same risk of developing these disorders. Individuals with peripheral obesity, i.e., fat distributed subcutaneously, are at little or no risk of the common medical complications of obesity, whereas individuals with central obesity, i.e., fat accumulated in visceral depots, are prone to these complications.
Evidence for a role of developmental genes in the origin of obesity and body fat distribution.
Sex, Age, Specimen part
View SamplesWe screened intronic microRNAs dysregulated in liver of obese mouse models to identify previously uncharacterized coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus. Our approach identified the expression of Ectodysplasin A (Eda), the causal gene of X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) was strongly increased in liver of obese mouse models both in rodents and humans.Eda expression in murine liver is controlled via PPAR? activation, increases in circulation and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. Consistently, bi-directional modulation of hepatic Eda expression in mouse models affects systemic glucose metabolism with alterations of muscle insulin signaling, revealing a novel role of EDA as an obesity-associated hepatokine, which impairs insulin sensitivity in skeletal muscle. Overall design: Soleus muscle mRNA profiles of db/db mice at 3 weeks after injection of AAV encoding shRNA targeting mouse Eda or the control scrambled shRNA sequence at the titer of 2-3x10e10 particles/body.
A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle.
Age, Specimen part, Subject
View SamplesPatients had low calorie diet weight reduction run in prior to the day of surgery. The human liver and subcutaneous fat tissue samples were obtained from 12 obese subjects undergoing bariatric surgery and then used for the mRNA expression analyses. Overall design: mRNA profiles of human liver and subcutaneous fat tissue samples were generated by RNA sequencing using Illumina HiSeq 2500.
Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance.
Age, Specimen part, Subject
View SamplesActivity-dependent gene expression is central for sculpting neuronal connectivity in the brain. Despite the importance for synaptic plasticity, a comprehensive analysis of the temporal changes in the transcriptomic response to neuronal activity is lacking. In a genome wide survey we identified genes that were induced at 1, 4, 8, or 24 hours following neuronal activity in the hippocampus.
Genome-wide profiling of the activity-dependent hippocampal transcriptome.
Sex, Age, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An immediate-late gene expression module decodes ERK signal duration.
Specimen part, Cell line
View SamplesWe integrate experimental data and mathematical modelling to unveil how ERK signal duration is relayed to mRNA dynamics.
An immediate-late gene expression module decodes ERK signal duration.
Cell line
View SamplesUnderstanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs), and further down to sub-TAD loop domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions. Here we present a novel parameter-free algorithm (CaTCH) that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation which is a simple and biologically relevant property. By applying CaTCH to published Hi-C datasets, we show that previously reported folding layers appear at different insulation levels. We demonstrate that although no structurally privileged folding level exists, TADs emerge as a functionally privileged scale defined by maximal enrichment of CTCF at boundaries, and maximal cell-type conservation. By measuring transcriptional output in embryonic stem cells and neural precursor cells, we show that TADs also maximize the likelihood that genes in a domain are co-regulated during differentiation. Finally, we observe that regulatory sequences occur at genomic locations corresponding to optimized mutual interactions at the scale of TADs. Our analysis thus suggests that the architectural functionality of TADs arises from the interplay between their ability to partition interactions and the genomic position of regulatory sequences. Overall design: The hybrid mouse ESC line F1-21.6 (129Sv-Cast/EiJ), previously described in (Jonkers et al., 2009), were grown on mitomycin C-inactivated MEFs in ES cell media containing 15% FBS (Gibco), 10-4 M b-mercaptoethanol (Sigma), and 1000U/ml of leukaemia inhibitory factor (LIF, Chemicon). Mouse ES cells were differentiated into neural progenitor cells (NPC) as previously described (Conti et al., 2005; Splinter et al., 2011). Total RNAs were prepared by Trizol extraction from the mouse ESC line, and for one NPC clone derived from it. Two biological replicates were collected for ESCs and NPCs. After ribosomal RNA depletion with Ribo-Zero (Illumina), RNA-seq libraries were prepared using ScriptSeq v2 kit (Illumina) following the manufacturer’s instructions. Libraries were prepared in two technical replicates per biological replicate. 50 bp single-end sequencing was performed on Illumina HiSeq 2000 instruments according to manufacturer’s instructions.
Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes.
Specimen part, Subject
View SamplesAberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific experimental conditions. Here we present PROGENy, a method that overcomes both limitations by leveraging a large compendium of publicly available perturbation experiments to yield a common core of Pathway RespOnsive GENes. Unlike existing methods, PROGENy can (i) recover the effect of known driver mutations, (ii) provide or improve strong markers for drug indications, and (iii) distinguish between oncogenic and tumor suppressor pathways for patient survival. Collectively, these results show that PROGENy accurately infers pathway activity from gene expression. Overall design: HEK293?RAF1:ER cells were treated with different stimuli (4OHT, Ly29002, TNFa, TGF1b, IFNg) for different periods of time (1h, 4h).
Perturbation-response genes reveal signaling footprints in cancer gene expression.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Cell line, Treatment
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