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SRP028932
Rattus norvegicus
47 Downloadable Samples
Illumina HiSeq 2000
Description
The metabolic syndrome (MetS) is a collection of co-occurring complex disorders including obesity, hypertension, dyslipidemia, and insulin resistance. The Lyon Hypertensive (LH) and Lyon Normotensive (LN) rats are models of MetS sensitivity and resistance, respectively. To identify genetic determinants and mechanisms underlying MetS, 169 rats from an F2 intercross between LH and LN were studied. Multi-dimensional data were obtained including genotypes of 1536 SNPs, 23 physiological traits including blood pressure, plasma lipid and leptin levels, and body weight/adiposity, and more than 150 billion nucleotides of RNA-seq reads from the livers of 36 F2 individuals, 6 LH and 6 LN individuals. We identified 17 pQTLs (physiological quantitative trait loci) and 1200 eQTLs (gene expression quantitative trait loci). Systems biology methods were applied to identify 18 candidate MetS genes, including genes (Prcp and Aqp11) previously shown to be MetS-related. We found an eQTL hotspot on RNO17, which was also located within pQTLs for MetS-related traits. The genes regulated by this eQTL hotspot were mainly in two co-expression network modules (a mitochondria related module and a gene regulation related module) and were predicted to causally affect many MetS-related traits. Multiple evidences strongly and consistently support RGD1562963, a gene regulated in cis by this eQTL hotspot and possibly related to RNA stability, as the eQTL driver gene directly affected by genetic variation between LH and LN rats; the expression of this gene is also correlated with MetS-related traits. Our study sheds light on the intricate pathogenesis of MetS and proved that systems biology with high-throughput sequencing is a powerful method to study the etiology of complicated diseases. Overall design: RNA-Seq of the liver of 6 LH (Lyon Hypertensive) rats and 6 LN (Lyon Normotensive) rats and 36 F2 rats.
Publication Title
Systems biology with high-throughput sequencing reveals genetic mechanisms underlying the metabolic syndrome in the Lyon hypertensive rat.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PPARG binding landscapes in macrophages suggest a genome-wide contribution of PU.1 to divergent PPARG binding in human and mouse.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages.
Publication Title
PPARG binding landscapes in macrophages suggest a genome-wide contribution of PU.1 to divergent PPARG binding in human and mouse.
Sample Metadata Fields
Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 14 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sir2 is an NAD+-dependent histone deacetylase, and is the founding member of a large, phylogentically conserved, family of such deacetylases called the Sirtuins. The budding yeast, Saccharomyces cerevisiae, harbors 4 paralogs of Sir2, known as Hst1, Hst2, Hst3, and Hst4. Reducing the intracellular NAD+ concentration is inhibitory for the Sirtuins, and raising the intracellular nicotinamide (NAM) concentration is inhibitory. Microarray gene expression analysis was used to identify novel classes of yeast genes whose expression is altered when either NAD+ concentration is reduced or NAM is elevated. A subset of genes involved in thiamine biosynthesis was identified as being upregulated when Sir2 or Hst1 was inactivated.
Publication Title
Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling.
Publication Title
LXR is a negative regulator of glucose uptake in human adipocytes.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
EphB receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. In addition, they can act as tumor promoters for adenoma development, but suppress progression to invasive carcinoma. Here we used imatinib to abrogate Abl kinase activity in ApcMin/+ mice and in mice with LGR5+ stem cells genetically targeted for APC. This treatment inhibited the tumor-promoting effects of EphB signaling without attenuating EphB-mediated tumor suppression, demonstrating the role of EphB signaling in intestinal tumor initiation. The investigated treatment regimen extended the lifespan of ApcMin/+ mice, and reduced cell proliferation in cultured slices of adenomas from FAP patients. These findings connect the EphB signaling pathway to the regulation of intestinal adenoma initiation via Abl kinase. Our findings may have clinical implications for pharmacological therapy against adenoma formation and cancer progression in patients predisposed to develop colon cancer.
Publication Title
An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
In order to define the targets of two miRNA overexpressed in NK cells in CFS/ME paitents, miRNA precursors for hsa-miR-99b and hsa-miR-330-3p were transfected in to buffy coat derived Natural Killer cells isolated by negative magnetic selection.
Publication Title
MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME).
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and re-populate the tumor. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and re-activation. In this study we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state which is switched on by engagement with bone lining cells or osteoblasts, and switched off by osteoclasts remodeling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy targeting dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Publication Title
Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 10 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Maize LEAFBLADELESS1 (LBL1) and Arabidopsis SUPPRESSOR OF GENE SILENCING3 (SGS3) play orthologous roles in the biogenesis of 21 nucleotide trans-acting short-interfering RNAs (tasiRNAs). The phenotypes conditioned by mutation of lbl1 and SGS3 are, however, strikingly different, suggesting that the activities of these small RNA biogenesis components, or the tasiRNAs and their targets might not be entirely conserved. To investigate the basis for this phenotypic variation, we compared the small RNA content between wild-type and lbl1 seedling apices. We show that LBL1 affects all major classes of small RNAs, and reveal unexpected crosstalk between tasiRNA biogenesis and other small RNA pathways regulating miRNAs, retrotransposons, and DNA transposons. We further identified genomic regions generating phased siRNAs, including numerous loci generating 22-nt phased small RNAs from long hairpin RNAs or overlapping antisense transcripts not previously described in other plant species. By combining both analyses, we identified nine TAS loci, all belonging to the conserved TAS3 family. Contrary to other plant species, no TAS loci targeted by a single miRNA were identified. Information from target prediction, RNAseq, and PARE analyses identified the tasiARFs as the major functional tasiRNAs in the maize vegetative apex where they regulate expression of ARF3 homologs. As such, divergence in TAS pathways is unlikely to account for the distinct phenotypes of tasiRNA biogenesis mutants in Arabidopsis and maize. Instead, the data suggests variation in the spatiotemporal regulation of ARF3, or divergence in its function, as a plausible basis for the dramatic phenotypic differences observed upon mutation of SGS3/lbl1 in Arabidopsis and maize. Overall design: An analysis of tasiRNA biogenesis, activity, and contribution to developmental phenotypes in the maize leaf. Data generated includes small RNA sequencing data and mRNA sequencing data. All data was generated in both wild type and lbl1 mutant maize leaf apices. Three replicates were generated for each genotype for the small RNA data. Two of these replicates were also used for the RNA-seq data.
Publication Title
Genome-wide analysis of leafbladeless1-regulated and phased small RNAs underscores the importance of the TAS3 ta-siRNA pathway to maize development.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
The peroxisome proliferator-activated receptor-coactivator-11 (PGC-11) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-11 activation has been suggested to be beneficial for systemic metabolism. Pharmacological PGC-11 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-11 is a transcriptional coactivator with no known ligand-binding activities. Importantly, PGC-11 activation is regulated by several mechanisms but protein stabilization is a limiting step as the protein has a short half-life under unstimulated conditions.
Publication Title
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Sample Metadata Fields
Specimen part
View Samples