Forkhead box class O (FoxO) transcription factors regulate whole body energy metabolism, skeletal muscle mass and substrate switching. To elucidate the role of FOXO in skeletal muscle, dominant negative (dn) constructs for FOXO1 (FOXO1dn) or FOXO3 (FOXO3dn) were transfected by electroporation into mouse tibialis anterior muscle and glucose uptake, signal transduction, and glucose stimulated gene expression profiles were assessed. Results were compared against contralateral control transfected muscle.
Regulation of glucose uptake and inflammation markers by FOXO1 and FOXO3 in skeletal muscle.
Sex, Age, Specimen part
View SamplesWe performed the circadian transcriptome analysis using the skeletal muscle from sedentary and exercised mice either in the early rest phase (ZT3) or in the early active phase (ZT15). By the combination with circadian transcriptomic and metabolomic analysis, we revealed time-of-day-dependent remodeling of circadian muscular metabolic pathways involved in glucose and glycerol metabolism after exercise. We found that only exercise in the early active phase elevates the levels of genes encoding glycolytic enzymes followed by the activation of fatty acid oxidation, branched-chain amino acid catabolism and ketogenesis/ketosis. This study demonstrates that time-of-day is a critical factor to modulate the impact of exercise on metabolic pathways within skeletal muscle. Overall design: Skeletal muscles from sedentary (sham-exercise) mice and mice subjected to acute treadmill exercise either in the early rest phase (ZT3) or in the early active phase (ZT15) were harvested after 0, 4, 8, 12, 16, and 20 hours after exercise or sham-exercise treatment.
Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesPrimordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals.
Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.
Specimen part
View SamplesMounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.
Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Specimen part
View SamplesPostnatal handling in rodents leads to decreased anxiety-like behavior in adulthood. We used microarrays to look at gene expression differences in the CA1 region of the hippocampus in female mice subjected to postnatal handling compared to controls.
Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.
No sample metadata fields
View SamplesGenetically identical inbred mice exhibit substantial stable individual variability in exploratory behavior. We used microarrays to look at gene expression differences in the hippocampus in female mice separated by stable differences in exploratory behavior
Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.
No sample metadata fields
View SamplesCD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogenactivated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer.
Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA.
Specimen part, Cell line
View SamplesAsthma is a heterogeneous disease. Exercise-induced bronchoconstriction (EIB) is a distinct syndrome that occurs in 30-50% of asthmatics and is characterized by high levels of pro-inflammatory eicosanoids. We identified genes differentially expressed in the airways of asthmatics with EIB relative to asthmatics without EIB. Genes related to epithelial repair and mast cell infiltration including beta-tryptase and carboxypeptidase A3 were upregulated by exercise challenge in the asthma group with EIB. We confirmed that two novel mediators trefoil factor 3 (TFF3) and transglutaminase 2 (TGM2) have increased expression in airways cells and secreted product in the airways. In vitro studies indicate that 1) TFF3 induces nitric oxide synthase in airway epithelial cells from asthmatics and 2) TGM2 augments the enzymatic activity of secreted phospholipase A2 (sPLA2) group X, an enzyme recently been implicated in asthma pathogenesis. Since PLA2 serves as the first rate-limiting step leading to eicosanoid generation, these results suggest that TGM2 may be a key initiator of the airway inflammatory cascade in asthma.
Transglutaminase 2, a novel regulator of eicosanoid production in asthma revealed by genome-wide expression profiling of distinct asthma phenotypes.
No sample metadata fields
View SamplesMyocardial infarction (MI) leads to activation of cardiac fibroblasts (aCFs) and at the same time induces the formation of epicardium-derived cells at the heart surface. To discriminate between the two cell populations, we elaborated a fast and efficient protocol for the simultaneous isolation and characterization of aCFs and epicardial stromal cells (EpiSCs) from the infarcted mouse heart. For the isolation of aCFs and EpiSCs, infarcted hearts (50 min ischaemia/reperfusion) were digested by perfusion with a collagenase-containing medium for only 8 min, while EpiSCs were enzymatically removed from the outside by applying mild shear forces via a motor driven device.
Novel technique for the simultaneous isolation of cardiac fibroblasts and epicardial stromal cells from the infarcted murine heart.
Specimen part
View SamplesThe discovery of fetal mRNA transcripts in maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma transcripts common to term pregnant women and their newborns but reduced or absent in the postpartum mothers.
Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood.
Specimen part
View Samples