The purpose of this study was to examined the acute actions of the second generation antipsychotic (SGA), olanzapine, on skeletal muscle (gastrocnemius) of Sprague Dawley Rats. SGAs cause metabolic side effects including leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. These effects are preceded by glucose intolerance and increased FFA flux and metabolism in peripheral tissues. Skeletal muscle is a likely target of glucose intolerance, therefore understanding how olanzapine affects the skeletal muscle transcriptome could elucidate approaches for mitigating these side effects. Male Sprague-Dawley rats freely fed on normal chow with comparable body weights (vehicle: 373±9g, olanzapine: 388±11g, p=0.34) were infused with vehicle or olanzapine for 24h using a dosing regimen leading to mild hyperglycemia (vehicle, 98±2mg/dl; olanzapine 127±4mg/dl, p=0.0023). For the olanzapine group, the venous catheter was attached to a syringe pump (Model NE-300) filled with olanzapine (Dr. Reddy’s Laboratories Ltd, Hyderabad, India) in sterile saline (infusion: 1mg/100g BW loading dose for 0.5h and then 0.04mg/100g/h continuously for 23.5h). Gastrocnemius was then surgically removed under isoflurane anesthesia (carried with 100% O2), and frozen between two aluminum blocks cooled to the temperature of liquid nitrogen and then stored at -80oC until RNA was isolated. With anesthesia gas flow continuing, the animals were euthanized by cutting the diaphram and removing the heart. The mRNA was isolated from from these muscles and used for RNA-Seq followed by alignment of the data with the rat genome assembly 5.0. To determine significant differences in FPKM values between control and olanzapine groups, the DEGexp function of the DEGseq 1.18.0 R package was used with the Likelihood Ratio Test (LRT) and default parameters. In the uploaded excel file, P values with p<0.05 and p<0.001 are shown for each row in different columns indicated by the number 1. The value 0 indicates the row is not significantly different. Overall design: Comparison of vehicle (n=3) and olanzapine infused (n=3) rats.
RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.
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View SamplesIn this study, we analyzed global liver gene expression in MICU1 knock-down (KD) mice. To generate liver-specific MICU1 KD mice, MICU1loxp/loxp male mice were treated with an AAV8-Cre under the control of a hepatocyte specific promoter (TBG). AAV8-TBG-Null treated littermates were used as controls. Liver samples were collected 3-5 weeks after injection. Knockdown was verified by protein and mRNA (94%, 98%, respectively). Mouse Gene 2.0 ST (Affymetrix, Santa Clara, CA) arrays were used to obtain global gene expression data.
MICU1 regulation of mitochondrial Ca(2+) uptake dictates survival and tissue regeneration.
Treatment
View SamplesMicroarray whole-transcriptome profiling in HCT116 and HepG2 cells treated with Melicope ptelefolia leaf extract reveals transcriptome profles exhibiting anticancer activity
Microarray gene expression profiling in colorectal (HCT116) and hepatocellular (HepG2) carcinoma cell lines treated with <i>Melicope ptelefolia</i> leaf extract reveals transcriptome profiles exhibiting anticancer activity.
Specimen part, Cell line, Treatment
View SamplesWe characterize histone crotonylation in intestinal epithelium-derived cells through Mass spectrometry, ChIp-Seq and RNA-Seq approaches and show that this modification is removed by class I histone deacetylases, HDAC1, 2 and 3. Overall design: RNA-Seq profile from mouse colon epithelium. ChIP-Seq experiments for H3K18crotonylation and H3K4me3 on mouse colon epithelium. ChIP-Seq experiments for H3K18 crotonylation and H3K18 acetylation on HCT116 cell line treated or not with the HDAC inhibitor MS275 (5 µM) for 18h. All the experiments were performed in triplicate.
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas.
Age, Specimen part
View SamplesPancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional approaches. In this study, we report that the histone deacetylase associated SIN3B protein is required for activated KRAS-induced senescence in vivo using a mouse model of pancreatic cancer.
Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression.
Specimen part
View SamplesNaive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are derived from the preimplantation epiblast and primordial germ cells (PGCs), respectively. We investigated whether differences exist between ESCs and EGCs, in view of their distinct developmental origins. PGCs are programmed to undergo global DNA demethylation; however, we find that EGCs and ESCs exhibit equivalent global DNA methylation levels. Importantly, inhibition of Erk and Gsk3b by 2i conditions leads to pronounced reduction in DNA methylation in both cell types. This is driven by Prdm14 and is associated with downregulation of Dnmt3a and Dnmt3b. However, genomic imprints are maintained in 2i, and we report derivation of EGCs with intact genomic imprints. Collectively, our findings establish that culture in 2i instills a naive pluripotent state with a distinctive epigenetic configuration that parallels molecular features observed in both the preimplantation epiblast and nascent PGCs.
Naive pluripotency is associated with global DNA hypomethylation.
Sex, Specimen part
View SamplesThe aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition, TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas.
Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.
No sample metadata fields
View SamplesThe p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in non-tumoral brain (NB) and grade I-IV gliomas. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBMs demonstrating the lowest RSK3 protein levels. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (RSK1hi) that excluded long-survivor cases expressed higher levels of RSK1. No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in glioblastomas (GBM) were associated with worse survival. RSK1hi and, to a lesser extent, RSK2hi GBMs, showed higher levels of phosphorylated RSK, which indicates RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated-natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long-survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker LAPTM5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration, suggests RSK1 as a potential progression marker and therapeutic target for gliomas.
Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration.
Specimen part
View SamplesEpithelial gland development within the uterine lining during prepubertal period is important to ensure successful gestation in adults. Lgr5 expression in uterus becomes largely restricted to the tips of developing glands after birth. These Lgr5 highly expressing cells function as stem cells during gland development.
Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development.
Specimen part
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