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SRP103000
Rattus norvegicus
39 Downloadable Samples
Illumina HiSeq 4000
Description
Studies have reported opposing effects of high-fat diet and mechanical stimulation on lineage commitment of the bone marrow stem cells. Yet, how the bone marrow modulates its gene expression in response to the combined effects of mechanical loading and a high-fat diet has not yet been addressed. We investigated whether early-life voluntary physical activity can modulate the effects of a high-fat diet on body composition, bone phenotype and bone marrow gene expression in male Sprague Dawley rats. We show that early-life high-fat diet positively affected body weight, total fat percentage and bone mass indices. In the bone marrow, early-life high-fat diet resulted in adipocyte hypertrophy and a pro-inflammatory and pro-adipogenic gene expression profile. Crucially, the bone marrow of the rats that undertook wheel exercise while on a high-fat diet retained a memory of the early-life exercise. This memory lasted at least 60 days after the cessation of the voluntary exercise and was manifest by: 1) the bone marrow adipocyte size of the exercised rats not exhibiting hypertrophy; and 2) genes associated with mature adipocyte function being down-regulated. Our results are consistent with the marrow adipose tissue having a unique and long-lasting response to high-fat feeding in the presence or absence of exercise. Overall design: Eighty male SD rats were randomised at weaning into : chow-fed group (C-SED) or a high-fat fed group. The high-fat fed group was further divided into three sub-groups: the high-fat sedentary (HF-SED) group, the high-fat late-exercise (HF-LEX) group, and the high-fat early-exercise (HF-EEX) group. At day 120-123, the animals were culled and total RNA was extracted from the bone marrow of the femur. The RNA was sequenced using Illumina Hiseq4000 technology. Differential gene expression analysis was carried out using Tuxedo suite of bioinformatic tools.
Publication Title
A Memory of Early Life Physical Activity Is Retained in Bone Marrow of Male Rats Fed a High-Fat Diet.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Sex, Age, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins, and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target of miR-29. In vitro radiolabeled acetate incorporation assays confirm that pharmacologic inhibition of miR-29 significantly reduces de novo cholesterol and fatty acid synthesis. Our findings indicate that miR-29 controls hepatic lipogenic programs, likely in part through regulation of Ahr and Sirt1, and therefore may represent a candidate therapeutic target for metabolic disorders such as dyslipidemia. Overall design: Hepatic mRNA profiles of C57BL/6J female mice treated with LNA against miR-29a, miR-29b and miR-29c versus saline.
Publication Title
Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Pancreatic cancer is characterized by heavy desmoplasia. Triptolide and its water-soluble pro-drug Minnelide are extremely efficient against pancreatic cancer in animal models. However, the effects of triptolide on pancreatic cancer stromal cells are largely unknown. The aim of this project is to indentify potential cellular functions that are affected by triptolide in pancreatic cancer associated fibroblasts. Overall design: Cancer associated fibroblasts were isolated from pancreatic tumor of KPC mouse model. Cells were either untreated or treated with 100nM triptolide for 6h or 24h before RNA isolation. The RNA was quality tested using a Bioanalyzer 2100 (Agilent Technologies, CA, USA). cDNA was created by reverse transcription of oligo-dT purified polyadenylated RNA and fragmented, blunt-ended, and then ligated to barcoded adaptors. Then, the library was size selected, and the selection process was validated and quantified by capillary electrophoresis and qPCR, respectively. Samples were load on the HiSeq 2500 (Illumina Inc., CA, USA) to generate around 25 million paired-end 50bp reads for each sample.
Publication Title
Inactivation of Cancer-Associated-Fibroblasts Disrupts Oncogenic Signaling in Pancreatic Cancer Cells and Promotes Its Regression.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
We examined the transcriptomes of murine "expandable hemangioblasts" (eHBs) and their blood and endothelial progeny, comparing them to the transcriptomes of murine embryonic stem (ES) cells, primary murine endothelial cells isolated from E11.5 yolk sacs or embryos, and E14.5 fetal liver hematopoietic stem cells. Overall design: Total RNAs were purified from lysates of cultured or primary cells, reverse transcribed, and sequenced on an Illumina HiSeq 2500.
Publication Title
An expandable, inducible hemangioblast state regulated by fibroblast growth factor.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
In our investigations of the molecular pathways of prostate tumorigenesis in Nkx3.1; Pten mutant mice using gene expression profiling, we now find that the AP-1 transcription factors, c-Jun and c-Fos, are significantly up-regulated during cancer progression. Forced expression of c-Fos and c-Jun in prostate cancer cells results in increased tumorigenicity, activation of Erk MAP kinase, and enhanced survival in the absence of androgens, which are hallmarks of disease progression. In humans, Jun and Fos proteins are significantly up-regulated during prostate cancer progression and significantly correlated with activation of Erk MAP kinase. Most notably, expression of Jun is associated with disease recurrence independent of other currently used prognostic indicators.
Publication Title
Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We quantified differential gene (mRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control.
Publication Title
HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-seq profiling was conducted on clinically-annotated human pancreatic adenocarcinoma cancer tissues Overall design: We measured the transcriptome in 51 clinically-annotated human pancreatic adenocarcinoma cancer tissues
Publication Title
RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4.
Sample Metadata Fields
Age, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The study was performed to determine if there were alterations in the total RNA pool among the epidermal keratinocytes of K14 promotor-driven noggin overexpression compared with K14 promotor-driven BMP4 overexpression transgenic animals, which will directly relate to cellular chemistry and immune and sensory function. The total study is also aimed at determining alterations of transcrption factors and/or regulation of gene function, including methylation states and micro RNA control in keratinocytes following sensory challenge, particularly neuropathic and chronic pain conditions.
Publication Title
Keratinocyte expression of calcitonin gene-related peptide β: implications for neuropathic and inflammatory pain mechanisms.
Sample Metadata Fields
Specimen part
View Samples