We performed a comparative, whole-transcriptome, analysis to identify stress-induced genes and relevant pathways that may be affected by sleep deprivation. Methods: One day following 12 hours of Paradoxical Sleep Deprivation (PSD), mice were restrained for 20 minutes. Gene expression changes in the pituitary were assessed via RNA-Seq and Gene Ontology in PSD and/or restrained groups compared to controls. Results: We show that restraint triggers transcriptional responses involved in hormone secretion, the glucocorticoid response, and apoptosis in both sexes, with 285 differentially expressed genes in females and 93 in males. When PSD preceded restraint stress, the numbers of differentially expressed genes increased to 613 in females and 580 in males. The pituitary transcriptome of restraint+PSD animals was enriched for microglia and macrophage proliferation, cellular response to corticosteroids, and apoptosis, among others. Finally, we show sex-specific differences in restraint-induced genes following PSD. Conclusion: The results indicate striking differences in the male and female stress-induced transcriptome, as well as in the PSD-induced changes. When PSD preceded the restraint stress challenge, the effects on the pituitary transcriptome were striking. While the male and female PSD + restraint-induced transcriptome was similar, we detected remarkable differences, perhaps indicating different strategies used by each sex to cope with challenges to homeostasis. We hope that these data illuminate future research elucidating how sleep deprivation impacts the vital response to stress and motivate the analysis of male and female subjects when designing experiments. Overall design: Gene expression changes in the pituitary were assessed via RNA-Seq and Gene Ontology in Paradoxical Sleep Deprivation and/or restrained groups compared to controls.
Sleep Deprivation Alters the Pituitary Stress Transcriptome in Male and Female Mice.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesThe ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life.
Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone.
Specimen part
View SamplesMicroarray analysis of total RNA isolated from samples of circulating tumor cells from 7 patients before romidepsin infusion (0 hours), at 4 h after initiation of the infusion (4 hours) and 24 h after initiation of the infusion (24 hours).
MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor resistance: rationale to combine romidepsin with an MEK inhibitor.
No sample metadata fields
View SamplesOvarian clear cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a genetically engineered mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumors with OCCC-like histopathology, culminating in hemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolonged mouse survival by inhibiting tumor cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signaling in OCCC pathogenesis. We further show that ARID1A-PIK3CA mutations cooperate to promote tumor growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodeling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signaling. We propose that ARID1A protects against inflammation-driven tumorigenesis.
Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.
Specimen part
View SamplesWe characterized the insulin sensitivity and multi-tissue gene expression profiles of lean and insulin resistant, obese Zucker rats untreated or treated with one of four PPAR ligands (pioglitazone, rosiglitazone, troglitazone, and AG035029). We analyzed the transcriptional profiles of adipose tissue, skeletal muscle, and liver from the rats and determined whether ligand insulin-sensitizing potency was related to ligand-induced alteration of functional pathways. Ligand treatments improved insulin sensitivity in obese rats, albeit to varying degrees.
Multi-tissue, selective PPARγ modulation of insulin sensitivity and metabolic pathways in obese rats.
Sex, Specimen part
View SamplesComparison of gene expression from subjects who resolved or formed pustules to H.ducreyi.
Dysregulated immune profiles for skin and dendritic cells are associated with increased host susceptibility to Haemophilus ducreyi infection in human volunteers.
No sample metadata fields
View SamplesThe process of lung squamous carcinoma tumorigenesis and metastasis is poorly characterized. Additionally, few models of this process exist in an immune-competent context. In order to address this problem, we utilized the KLN-205 lung squamous carcinoma cell lines that is derived from carcinogen exposure in DBA2 mice.
Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking.
Specimen part
View SamplesUpon immunization with a T cell dependent antigen naive follicular B cells (Fo) are activated and a germinal center reaction is induced. Within the next 2 weeks large germinal centers develop where the process of affinity maturation takes place. To analyze the gene expression profile of resting and activated B cells, follicular B cells (Fo), B cells from early (GC1) and late germinal centers (GC2) were isolated and their gene expression profile compared.
In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3(hi) stromal cells isolated from SCID mice.
Sex, Specimen part
View SamplesMicroarrays were used to analyze differential gene expression and to help determine the efficacy of Iressa (gefitinib), a tyrosine kinase inhibitor, on endometrial cancer cells.
EGFR isoforms and gene regulation in human endometrial cancer cells.
Specimen part, Cell line
View SamplesThe use of alternative polyadenylation sites is common and affects the post-transcriptional fate of mRNA, including its stability, localization, and translation. Here we present a method for genome-wide and strand-specific mapping of poly(A) sites and quantification of RNA levels at unprecedented efficiency by using an on-cluster dark T-fill procedure on the Illumina sequencing platform. Our method outperforms former protocols in quality and throughput, and reveals new insights into polyadenylation in Saccharomyces cerevisiae. Overall design: Experimental benchmark of five different protocols (3tfill, bpmI, internal, rnaseq and yoon) for genome-wide identification of polyadenylation sites in Saccharomyces cerevisiae and transcript quantification. RNA was extracted from WT cells grown in glucose (ypd) or galactose (ypgal) as carbon source. The same RNA was used for 3 independent library constructions (technical replicates, rep).
An efficient method for genome-wide polyadenylation site mapping and RNA quantification.
Cell line, Subject
View Samples