Expression quantitative trait loci (eQTL) analyses were conducted separately on the glomerular and tubular portions of healthy human kidney samples obtained from subjects of European descent. Overall design: We aimed to define genotype driven gene expression changes in the glomerular and tubular compartments of human kidneys, identifying genetic variants (eVariants) that influence the expression of genes (eGenes). Later, we integrated this information with genotype and phenotype association studies (GWAS) to identify genes for which expression in the kidney shows differences in patients with GWAS variants.
Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.
Specimen part, Disease, Disease stage, Subject
View SamplesMultiple myeloma is a fatal hematological malignancy. In order to develop effective therapeutic approaches, it is critical to understand the pathogenesis of myeloma. The Radl 5T model of multiple myeloma is a clinically relevant murine model where myeloma spontaneously occurs in aged, in-bred C57BlKalwRij mice and can be propagated by intravenous inoculation of 5T myeloma cells into mice of the same strain. Importantly inoculation of 5T myeloma cells into C57Bl6 mice does not result in myeloma, demonstrating that the bone marrow (BM) microenvironment of the C57BlKalwRij strain provides a unique and permissive milieu for myeloma development. We hypothesized that cells of the BM microenvironment may provide essential stimuli for the development of multiple myeloma in vivo. We aim to determine the differences in expression within the bone marrow of C57Bl/KalwRij mice.
Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease.
No sample metadata fields
View SamplesThe gene encoding a protein (AmGSTF1) associated with multiple herbicide resistance (MHR) in black-grass was transgenically expressed in Arabidopsis thaliana.The goal of this study was to determine if AmGSTF1 could elicit an MHR phenotype in the transgenic host.
Key role for a glutathione transferase in multiple-herbicide resistance in grass weeds.
Specimen part
View SamplesThe FBXL10 protein (also known as KDM2B, JHDM1B, CXXC2, and NDY1) is bound to essentially all CpG-rich promoters in the mammalian genome. FBXL10 is expressed as two isoforms: FBXL10-1, a longer form that contains an N-terminal JmjC domain with C- terminal F-box, CXXC, PHD, RING, and leucine rich repeat (LRR) domains, and FBXL10-2, a shorter form that initiates at an alternative internal exon and which lacks the JmjC domain but retains the other domains. Selective deletion of Fbxl10-1 had been reported to produce a minor and variable phenotype, and most mutant animals were essentially normal. We show here that deletion of Fbxl10-2 (in a manner that does not perturb expression of Fbxl10-1) resulted in a very different phenotype with craniofacial abnormalities, greatly increased lethality, and female sterility in surviving homozygous mutants. The phenotype of the Fbxl10-2 deletion was more severe in female mutants. We found that mutants that lacked both FBXL10-1 and -2 showed embryonic lethality and even more extreme sexual dimorphism, with more severe gene dysregulation in mutant female embryos. X-linked genes were most severely dysregulated, and there was marked overexpression of Xist in mutant females although genes that encode factors that bind to Xist RNA were globally down-regulated in mutant female as compared to male embryos. FBXL10 is the first factor shown to be required both for the normal expression and function of the Xist gene. Overall design: Expression analysis using RNA-seq was performed on WT and Fbxl10T/T male and female embryos.
Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10.
Sex, Specimen part, Cell line, Subject
View SamplesDifferent wheat cultivars may be classified as either winter or spring varieties depending on whether they require exposure to an extended period of cold in order to become competent to flower. Using a growth regime that mimics the conditions that occur during a typical winter in Britain, we wished to survey the genes that are involved in phase transition as well as those involved in cold-acclimation.
Cold- and light-induced changes in the transcriptome of wheat leading to phase transition from vegetative to reproductive growth.
No sample metadata fields
View SamplesGenes relevant to manifestion of and variation in aggression behavior might be differentially expressed in lines selected for divergent levels of aggression.
Quantitative genomics of aggressive behavior in Drosophila melanogaster.
No sample metadata fields
View SamplesWe report gene expression in human neutrophils isolated by two methods: Polymorphprep (~95% purity) and negative selection (~99% purity) from two healthy donors - one donor with low eosinophil contamination of neutrophils and one donor with high eosinophil contamination of neutrophils. We report the effect of the presence of contaminating leukocytes in neutrophil preparations, and in reponse to inflammatory cytokines TNF-alpha and GM-CSF. Overall design: Healthy human neutrophils were isolated using Polymorphprep or negative selection, and incubated for 1h in the absence or presence of TNF-alpha or GM-CSF. RNA was analysed by Illumina HiSeq 2000. The results from n=2 donors were analysed as biological replicates for differential expression analysis.
Whose Gene Is It Anyway? The Effect of Preparation Purity on Neutrophil Transcriptome Studies.
No sample metadata fields
View SamplesInvolution returns the lactating mammary gland to a quiescent state after weaning. The mechanism of involution involves collapse of the mammary epithelial cell compartment. To test whether the cJUN NH2-terminal kinase (JNK) signal transduction pathway contributes to involution, we established mice with JNK deficiency in the mammary epithelium. We found that JNK is required for efficient involution. JNK deficiency did not alter the STAT3/5 or SMAD2/3 signaling pathways that have been previously implicated in this process. Nevertheless, JNK promotes the expression of genes that drive involution, including matrix metalloproteases, cathepsins, and BH3-only proteins. These data demonstrate that JNK has a key role in mammary gland involution post lactation. Overall design: WAP-Cre and Jnk1f/f Jnk2f/f WAP-Cre mice were bred for a single pregnancy and litters were normalized to 6-8 pups. The pups were allowed to nurse for 9 days before forced weaning. At that point, some mice were euthanized and their mammary glands were harvested to isolate RNA (0 days). Other mice were kept for 3 days before euthanasia and mammary gland harvest (3d). In this way, gene expression differences could be determined between JNK-null and JNK-wildtype mammary glands before and during involution.
The cJUN NH<sub>2</sub>-terminal kinase (JNK) pathway contributes to mouse mammary gland remodeling during involution.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ACTH is a potent regulator of gene expression in human adrenal cells.
No sample metadata fields
View SamplesMembers of the JNK pathway have been found to be mutated in human breast cancer. Mouse studies examining JNK loss in different tissues have demonstrated that the JNK pathway can play a role in cancer. Using and autochthonous mouse model, we found that JNK deficiency on a p53-null background resulted in more rapid tumor onset. To learn more about these tumors we generated cells lines and performed various in vitro assays, as well as RNAseq in hope of finding differentially expressed genes that may explain the differences we observed in vivo. Overall design: Tumors were harvested from mice and cells lines were established from them. RNA was isolated from established tumor cell lines.
The cJUN NH<sub>2</sub>-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation.
Cell line, Subject
View Samples