Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes, however, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and muscle molecular circadian clock have never been investigated in humans. Here we investigated insulin sensitivity and muscle metabolism in fourteen healthy young lean men (age 22.4 2.8 years; BMI 22.3 2.1 kg/m2 [mean SD]) after a 3-day control protocol and a 3.5-day misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that circadian misalignment results in a significant decrease in peripheral insulin sensitivity due to a reduced skeletal muscle non-oxidative glucose disposal (Rate of disappearance: 23.7 2.4 vs. 18.4 1.4 mg/kg/min; control vs. misalignment; p=0.024). Fasting glucose and FFA levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the new behavourial rhythm, and microarray analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misallignement. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.
Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle.
Sex, Subject
View SamplesMicroarray analysis of gene expression after transverse aortic constriction in mice: comparison of TAC vs. sham group at 48 hours, 10 days, and 3 weeks.
Microarray analysis of gene expression after transverse aortic constriction in mice.
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View SamplesInhibiting tafazzin a cardiolipin remodeling enzyme reduces stemness of AML by modulating the level of phosphatidylserine Overall design: Gene expression analysis upon knock-down of TAZ by two independent shRNAs
The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.
Specimen part, Cell line, Subject
View SamplesASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice, however, the underlying molecular mechanisms remain unclear. Here, we report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromotid segregation and to regulate gene expression. Loss of Asxl1 impairs the cohesin function as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. ChIP-seq data revealed that ASXL1, RAD21 and SMC1A share 93% of genomic binding sites at promoter regions in lineage-cKit+ (LK) cells. We have showed that loss of Asxl1 reduced the genome binding of RAD21 and SMC1A, and altered the expression of ASXL1/cohesin target genes in LK cells. Our study underscores the ASXL1-cohesin interaction as a novel means to maintain normal sister chromatid separation and to regulate gene expression in hematopoietic cells. Overall design: The DEG genes'' relation with the changes of ASXL1 peaks and Cohesin peaks changes
ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis.
Specimen part, Cell line, Subject
View SamplesIn the developing brain, heightened plasticity during the critical period enables the proper formation of neural circuits. Here we identify the “navigator” neurons, a group of perinatally born olfactory sensory neurons, as playing an essential role in establishing the olfactory map during the critical period. The navigator axons project circuitously in the olfactory bulb and traverse multiple glomeruli before terminating in perspective glomeruli. These neurons undergo a phase of exuberant axon growth and exhibit a shortened lifespan. Single cell transcriptome analyses reveal distinct molecular signatures for the navigators. Extending their lifespan prolongs the period of exuberant growth and perturbs axon convergence. Conversely, genetic ablation experiment indicates that, despite postnatal neurogenesis, only the navigators are endowed with the ability to establish a convergent map. The presence and the proper removal of the navigator neurons are both required to establish tight axon convergence into the glomeruli. Overall design: 10X scRNA-seq was preformed on 4 samples of 4 ages of the olfactory epethelium of CD-1 mice. These ages were postanatal days 0, 3, 7, 21.
A Population of Navigator Neurons Is Essential for Olfactory Map Formation during the Critical Period.
Specimen part, Cell line, Subject
View SamplesThe anaerobic metabolism of the opportunistic pathogen Pseudomonas aeruginosa is important for growth and survival during persistent infections. The two Fnr-type transcription factors Anr and Dnr regulate different parts of the underlying network. Both are proposed to bind to a non-distinguishable DNA sequence named Anr box.
Anaerobic adaptation in Pseudomonas aeruginosa: definition of the Anr and Dnr regulons.
No sample metadata fields
View Samples3 pairs of wt and ClC-6 knockout mice, RNA from p14 hippocampus
Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.
Sex, Age, Specimen part, Subject, Time
View SamplesmRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Age, Specimen part, Treatment, Subject, Time
View SamplesThe constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcino- genesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARKO -PXRKO ), double humanized CAR and PXR (CARh - PXRh), and wild-type C57BL/6 mice. Wild-type and CARh-PXRh mouse livers exhibited temporally and quantitatively similar tran- scriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were ob- served with peak expression occurring between 1 and 7 days PB ex- posure. All these transcriptional responses were absent in CARKO- PXRKO mouse livers and largely reversible in wild-type and CARh - PXRh mouse livers following 91 days of PB exposure and a subse- quent 4-week recovery period. Furthermore, PB-mediated upregu- lation of the noncoding RNA Meg3, which has recently been associ- ated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARh-PXRh mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Age, Specimen part, Treatment, Subject, Time
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