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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
- 7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MYB plays a critical role as a regulator of erythropoieisis. We have shown that MYB silences epsilon and gamma-globin expression in erythroid progenitors. We here examine erythroid cells at the basophilic erythroblast stage of differentiation with MYB shRNA or control lentiviral transduction prior to differentiation.
Publication Title
MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4+ Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the Treg gene signature. Its ablation leads to severe immune deficiencies in human and mice. Recent developments in sequencing technologies have revolutionized the possibilities to gain insights into transcription factor binding by ChiP-Seq and into transcriptome analysis by mRNA-Seq. We combine FoxP3 ChiP-Seq and mRNA-Seq in order to understand the transcriptional differences between primary human CD4+ T helper and regulatory T-cells, as well as to study the role of FoxP3 in generating those differences. We show, that mRNA-Seq allows analyzing the transcriptomal landscape of T-cells including the expression of specific splice variants at much greater depth than previous approaches, whereas 50% of transcriptional regulation events have not been described before by using diverse array technologies.
Publication Title
Next-generation insights into regulatory T cells: expression profiling and FoxP3 occupancy in Human.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 22 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
The original objectives of the study were to identify surface markers specifically expressed in motor neurons. We now use the data to profile the expression of Cdk family members in motor neurons.
Publication Title
Dual Inhibition of GSK3β and CDK5 Protects the Cytoskeleton of Neurons from Neuroinflammatory-Mediated Degeneration In Vitro and In Vivo.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Wiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis.
Publication Title
An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Exercise has a positive effect on overall health. This study was performed to get an overview of the effects of mixed exercise training on skeletal muscl
Publication Title
Identification of human exercise-induced myokines using secretome analysis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from 7 nickel-allergic patients and 5 non-allergic controls at four different time points during elicitation of eczema: 0h, 7h, 48h and 96h. Each gene expression profile was analysed by hybridization to high density oligonucletide arrays.
Publication Title
Gene expression time course in the human skin during elicitation of allergic contact dermatitis.
Sample Metadata Fields
No sample metadata fields
View Samples