Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling.
Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation.
Specimen part
View SamplesPpargc1a overexpression in heart tissue measured using RNA sequencing Overall design: RNA expression profiles were generated using RNA-seq from control (N=3) and Ppargc1a overexpressing (N=3) mice
Peroxisome proliferator-activated receptor-γ coactivator 1 α1 induces a cardiac excitation-contraction coupling phenotype without metabolic remodelling.
Specimen part, Treatment, Subject
View SamplesWe recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations prior to wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Overall design: Lewis Lung Carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2, 3, or 4 wks and compared to PBS injected control. Muscle wasting was evident at 4 wks LLC. Animals were anesthetized using isoflourane and gastrocnemius muscles were collected for analysis. Conclusions: Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.
Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice.
Specimen part, Cell line, Subject
View SamplesAn alternative promoter of the PGC-1alpha gene gives rise to three new PGC-1alpha isoforms refered to as PGC-1a2 (A2), PGC-1a3 (A3) and PGC-1a4 (A4). The proximal PGC-1 alpha promotor transcribes the canonical PGC-1 alpha which is refered to as PGC-1a1 (A1).G1/G2/G3 samples refer to the Green fluorescent protein (GFP) control samples used in this experiment. Forced expression of the PGC-1a4 isoform results in muslce hypertrophy associated with increased IGF-1 signaling and repression of myostatin signaling.
A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy.
Specimen part
View SamplesThe peroxisome proliferator-activated receptor-coactivator-11 (PGC-11) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-11 activation has been suggested to be beneficial for systemic metabolism. Pharmacological PGC-11 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-11 is a transcriptional coactivator with no known ligand-binding activities. Importantly, PGC-11 activation is regulated by several mechanisms but protein stabilization is a limiting step as the protein has a short half-life under unstimulated conditions.
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomics of TGF-beta1 signaling in stem cell commitment and dendritic cell development.
No sample metadata fields
View SamplesLysine 9 di-methylation and lysine 27 tri-methylation of histone H3 (H3K9me2 and H3K27me3) are mostly linked to gene repression. However, functions of repressive histone methylation dynamics during inflammatory responses remain poorly understood. Here, we show that lysine demethylase 7A (KDM7A) and 6A (UTX) are rapidly transported to nuclear factor kappa-B (NF-?B) related elements in human endothelial cells in response to tumor necrosis factor (TNF)-a. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and cooperatively activate NF-?B dependent inflammatory genes. Furthermore, using both in situ Hi-C and other 3C based technology, loops between super enhancers (SEs) are newly formed following TNF-a-stimuli at NF-?B-dependent inflammatory loci where KDM7A- and UTX-recruitment coincide. Collectively, these findings suggest that erasing of repressive histone marks by KDM7A and UTX within NF-?B-related elements might functionally associate with formation of SE-SE three-dimensional interactions and could be a cue signal during inflammatory responses in human endothelial cells. Overall design: Total 29 samples were derived from [1] HUVECs in the absence or presence of TNF-alpha (0, 4, and 24 hrs) to determine TNF-alpha-responsive genes during inflammation, [2] si control, siKDM7A, siUTX, or siKDM7A+siUTX transfected HUVECs under TNF-alpha-stimuli (4 hrs) to understand molecular function of KDM7A and UTX during inflammation.
Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells.
Subject, Time
View SamplesRecently the role of PPAR/ in angiogenesis has been revealed, and we hypothesized that the crosstalk between hypoxia and PPAR/ on endothelial cells may exsist. To elucidate the interaction between two signalings, we report the comprehensive change of transcripts induced by PPAR/ agonist (GW501516) and/or hypoxia.
Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements.
Specimen part
View SamplesRNA-sequencing for 6 samples Overall design: Examing 2 conditions, each with 3 replicates
Integrated analysis of long non-coding RNAs and mRNAs associated with peritendinous fibrosis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of a novel gene for diabetic traits in rats, mice, and humans.
Sex, Age, Specimen part
View Samples