Gene expression was studied in whole kidneys in a 2 x 2 design. SBH/y were contrasted with SBN/y under basal conditions and after salt loading. Thus, four groups were studied altogether. Five rats were used in each group. Altogether, 20 animals were used, and each animal was studied separately. Gene expression was done in kidney. Differential gene expression was measured 4 weeks after initiation of salt loading. At that time point hypertension invariably evolves fully in SBH/y but not in SBN/y.<br></br><br></br>Affymetrix CHP files are available on request from arrayexpress@ebi.ac.uk
Identification of hypertension-related genes through an integrated genomic-transcriptomic approach.
Sex, Age, Specimen part, Cell line, Subject, Compound
View SamplesThis study was designed to investigate gene expression in kidneys of adult female Sabra rats (SBH/y and SBN/y rat strains) with two indwelling kidneys or after uni-ninephrectomy, seeking those genes that are differentially expressed between the two strains, and between animals with one or two kidneys. SBH/y after uninephrectomy develop proteinuria to a much greater extent than SBN/y. The study was performed as part of an overall effort to detect the genes that are associated with the pathophysiology of proteinuria.
Geno-transcriptomic dissection of proteinuria in the uninephrectomized rat uncovers a molecular complexity with sexual dimorphism.
No sample metadata fields
View SamplesEmbryonic stem cells (ESCs) cells run a self-renewal gene expression program, requiring the expression of certain transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs remains enigmatic. Here we show that Cohesin exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of the cohesin subunit Rad21 reveal an ESC specific cohesin binding pattern that is characterized by a CTCF independent colocalization of cohesin with pluripotency related transcription factors. Upon ESC differentiation, these binding sites disappear and instead new CTCF independent Rad21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of cohesin subunits causes expression changes that are reminiscent of the depletion of key pluripotency transcription factors, demonstrating the functional relevance of the cohesin - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin interacting proteins Stag1 and Wapl, further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program.
RAD21 cooperates with pluripotency transcription factors in the maintenance of embryonic stem cell identity.
Specimen part
View SamplesLong non-coding RNAs (lncRNAs) regulate diverse biological pathways. Unlike protein coding genes, where methods to comprehensibly study their functional roles in cellular systems are available, techniques to systematically investigate lncRNAs have largely remained unexplored. Here, we report a technology for combined Knockdown and Localization Analysis of Non-coding RNAs (c-KLAN) that merges phenotypic characterization and localization approaches to study lncRNAs. Using a library of endoribonuclease prepared short interfering RNAs (esiRNAs) coupled with a pipeline for synthesizing labeled riboprobes for RNA fluorescence in situ hybridization (FISH), we demonstrate the utility of c-KLAN by identifying a novel transcript Panct1 (Pluripotency associated non-coding transcript 1) that regulates embryonic stem cell identity. We postulate that c-KLAN should be generally useful in the discovery of lncRNAs implicated in various biological processes.
Combined RNAi and localization for functionally dissecting long noncoding RNAs.
Specimen part
View SamplesBy means of 3' end sequencing we provide a genome-wide, high-resolution polyadenylation map of the human heart. By sequencing 5 control en 5 dilated cardiomyopathy (DCM) myocardial specimens we investigate the difference in alternative polyadenylation (APA) in healthy and diseased hearts.
Genome-Wide Polyadenylation Maps Reveal Dynamic mRNA 3'-End Formation in the Failing Human Heart.
No sample metadata fields
View SamplesObjectives: Systemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of these responses we assessed inflammation and acute-phase response at early and late time points in muscle of patients at risk for CIM.
Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy.
Sex, Age, Specimen part, Disease, Subject
View SamplesTo monitor global transcript changes after Paf1C depletion we transfected ESCs with esiRNA targeting Ctr9 and control esiRNA (Luc).
A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1 complex for embryonic stem cell identity.
No sample metadata fields
View SamplesLeft ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.
Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
Sex, Age, Specimen part
View SamplesAcute liver injury is a critical life-threatening event. Common causes are infections, intoxication, and ischemic conditions. The cytokine Interleukin 22 (IL-22) has been implicated in this process. However, the role of IL-22 during acute liver damage is controversial, since both protective and pathogenic properties have been reported. IL-22 binding protein (IL-22BP, IL-22Ra2), a soluble endogenous inhibitor of IL-22, is able to regulate IL-22 activity, and thus might explain some of the controversial findings. Since the role of IL-22BP in liver injury is unknown, we used Il22bp deficient mice and mouse models for acute liver damage to address this point. We found that Il22bp deficient mice were more susceptible to ischemia- and acetaminophen- induced liver damage. Deficiency of Il22bp caused increased hepatic damage and delayed liver regeneration. Using an unbiased approach, we found that IL-22, if uncontrolled in Il22bp deficient mice, induced Cxcl10 expression by hepatocytes, thereby recruiting inflammatory CD11b+Ly6C+ monocytes into the liver upon liver damage. Accordingly, neutralization of Cxcl10 reversed the increased disease susceptibility of Il22bp deficient mice. In conclusion, our data suggest dual functions of IL-22 in acute liver damage, and highlight the need to control IL-22 activity via IL-22BP. Overall design: RNA sequencing of RNA isolated from liver tissue from mice that underwent liver reperfusion treatment (IR) or sham surgery, in triplicate for three genotypes (Wt, Il22-/- and Il22bp-/-).
A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury.
Specimen part, Treatment, Subject
View SamplesWe adopted the STRT-seq [Islam et al., Nat Methods 11, 163-166 (2013)] RNA-seq technology to a 9600-well array and applied it to analyze single cells from mouse and human cortex single cells. Overall design: 2192 single cells from mouse somatosensory cortex and 2028 single nuclei from human post-mortem middle temporal gyrus cortex.
STRT-seq-2i: dual-index 5' single cell and nucleus RNA-seq on an addressable microwell array.
No sample metadata fields
View Samples