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Mus musculus
27 Downloadable Samples
Illumina HiSeq 2000
Description
A few reports have implicated specific lncRNAs in cardiac development or failure, but precise details of lncRNAs expressed in hearts and how their expression may be altered during embryonic heart development or by adult heart disease is unknown. By comparing lncRNA profiles of normal embryonic (~E14), normal adult, and hypertrophied adult hearts we defined a distinct fetal lncRNA abundance signature that includes 157 lncRNAs differentially expressed compared to adults (fold-change = 50%, FDR=0.02), and which was only poorly recapitulated in hypertrophied hearts (17 differentially expressed lncRNAs; 13 of these observed in embryonic hearts). Analysis of protein-coding mRNAs from the same samples identified 22 concordantly and 11 reciprocally regulated mRNAs within 10 kb of dynamically expressed lncRNAs, reciprocal relationships of lncRNA and mRNA levels was validated for the Mccc1 and Relb genes using in vitro lncRNA knockdown in C2C12 cells. Network analysis suggested a central role for lncRNAs in modulating NFkappaB- and CREB1-regulated genes during embryonic heart growth and identified multiple mRNAs within these pathways that are also regulated, but independently of lncRNAs. Overall design: Cardiac polyadenylated RNA (mRNA and lncRNA) profiles were generated from C57BL/6J mouse hearts were generated on Illumina HiSeq 2000 instruments. 7 independent E13.5 hearts, 12 adult hearts (6 at 6 weeks of age, 6 at 16 weeks of age), 4 sham-operated hearts at 12 weeks of age, and 4 hearts after 4 weeks of pressure overload (TAC) at 12 weeks of age.
Publication Title
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Cells from three adult, wild-type, FVB hearts were separated into cardiomyocyte and nonmyocyte fractions using Langendorff perfusion, collagenase digestion and gravity filtration. Total RNA was prepared immediately from myocytes, while nonmyocytes were passaged twice to yield a culture from which total RNA was prepared. Overall design: 6 cardiac polyadenylated RNA (mRNA and lncRNA) and small RNA (microRNA) profiles of isolated cardiomyocytes (CM) and nonmyocytes (fibro) from 12-wk FVB/NJ mouse hearts were generated on Illumina HiSeq 2000 instruments.
Publication Title
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Next-generation sequencing (NGS) provides for quantitation of RNA abundances and comparison of RNA abundances within tissues and cells in a manner not possible with previous microarray technologies. 5 female mice were subjected to a sham operation, and 5 female mice were subjected to transverse aortic constriction (TAC). After 1 week, hearts were harvested and polyadenylated RNAs were profiled. Analyzed data have been published in Hu et al., Proc Natl Acad Sci USA. 2012;109(48):19864-9, PMID: 23150554 Overall design: 10 cardiac polyA+-RNA profiles of 9 week-old FVB/NJ wild type (WT) mice (5 female sham, 5 female TAC) were generated on Illumina HiSeq 2000 instruments.
Publication Title
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atopic dermatitis (AD) is a common disease, with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in lack of specific treatments. The prevailing view is that AD is a biphasic, T-cell polarized disease, with Th2 predominating acute AD, and a switch to Th1 characterizing chronic disease. Identification of factors that participate in onset of lesions and maintenance of chronic lesions is critical for development of targeted therapeutics. We performed global genomic, molecular and cellular profiling of paired non-lesional, acute, and chronic skin biopsies from ten AD patients. Onset of acute lesions is associated with a striking increase in a subset of terminal differentiation proteins, specifically the IL-22-modulated S100A7-9. Correspondingly, acute disease is associated with significant increases in gene expression levels of the major Th22- (IL-22) and Th2- (IL-4, IL-31) cytokines and Th17-regulated genes (CCL20, PI3/Elafin), without significant changes in IL-17. A lesser induction of Th1- (IFN, MX-1, CXCL9-11) associated genes was detected in acute disease. Chronic skin lesions are characterized by significantly intensified activation of Th22, Th2 and Th1. Our data establish increased expression of S100A7-9 and other epidermal genes at onset of acute AD, with parallel activation of Th2 and Th22 cytokines. Our findings suggest an absence of switch mechanism in chronic disease and instead indicate that progression to chronic lesions is associated with intensified activation of immune axes that initiate onset of acute lesions, particularly Th22 and Th2. This alters the prevailing view of pathogenesis, with important therapeutic implications.
Publication Title
Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis.
Sample Metadata Fields
Age, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders. Hypocretin (orexin) containing neurons of the lateral hypothalamus are clearly essential for the normal regulation of sleep and wake behaviors, and have been implicated in feeding, anxiety, depression and reward. However, little is known about the molecular phenotypes of these cells, or the mechanism of their specification. We have generated a Hcrt bacTRAP line for comprehensive translational profiling of these neuronsin vivo. From this profile, we have identified 188 transcripts, as enriched in these neurons, in additions to thousands more moderately enriched or nominally expressed. We validated many of these at the RNA and protein level, including the transcription factor Lhx9. Lhx9 protein is found in a subset of these neurons, and ablation of these gene results in a 30% loss of Hcrt neuron number, and a profound hypersomnolence in mice.This data suggests that Lhx9 may be important for specification of some Hcrt neurons, and the subsets of these neurons may contribute to discrete sleep phenotypes.
Publication Title
Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
After 2 and 12 weeks of treatment, we observed significant reductions of 51% and 72%, respectively, in SCORAD scores. Clinical improvements were associated with significant gene expression changes in lesional but also nonlesional skin, particularly reductions in levels of TH2-, TH22-, and some TH17-related molecules (ie, IL-13, IL-22, CCL17, S100As, and elafin/peptidase inhibitor 3), and modulation of epidermal hyperplasia and differentiation measures.
Publication Title
Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology.
Sample Metadata Fields
Sex, Age, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Interplay between metabolic state of the cell and its ability to undergo immunological activation has been recently recognized as a treasure chest of novel fundamental regulatory principles. Itaconate, and its membrane permeable derivative dimethyl itaconate (DI) were recently shown to selectively inhibit subset of cytokines during macrophage activation (e.g. Il1b, il6, Il12b but not TNF), yet the precise mechanism of this effect remained unclear. We find that selectivity of DI action stems from the inhibitory effects of electrophilic stress exerted by DI on IkB-zeta protein translation, leading to selective control of the secondary wave of Nfkb-signaling. Mechanistically, DI leads to glutathione depletion and subsequent activation of both Nrf2-dependent and Nrf2-independent stress responses. We find that IkB-zeta regulation is carried out in Nrf2-independent manner, and identify Atf3 as a key mediator of DI effects on IkB-zeta/IL6. This inhibitory effect is conserved across species and cell types, as evident from inhibition of IkB-zeta production in activating human monocytes and IL-17A stimulated keratinocytes of both human and mice. Finally, DI administration in vivo ameliorated IL17/IkB-zeta-driven skin pathology in the mouse model of psoriasis, highlighting therapeutic potential of this regulatory pathway. Overall design: Bone marrow-derived macrophages (BMDMs) from WT and Nrf2–/– mice were derived in 7 days in MCSF supplemented complete RPMI. Some samples cells were stimulated with 250 uM DimethylItaconate(DI) for 12 hours prior to collection for RNA-seq.
Publication Title
Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples
GSE85473- Drosophila melanogaster
- 16 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Anti-TNF-alpha therapy has made a significant impact on the treatment of psoriasis. Despite being designed to neutralize TNF-alpha activity, the mechanism of action of these agents in the resolution of psoriasis remains unclear. The aim of this study was to better understand the mechanism of action of etanercept by examining very early changes in the lesional skin of psoriasis patients. 20 chronic plaque psoriasis patients were enrolled and received 50mg etanercept twice weekly. Skin biopsies were obtained before treatment and on days 1, 3, 7 and 14 post-treatment. Skin mRNA expression was analysed by microarray.
Publication Title
Early tissue responses in psoriasis to the antitumour necrosis factor-α biologic etanercept suggest reduced interleukin-17 receptor expression and signalling.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Comparison of transcriptome between control and Tcf1/Lef1-deficient hematopoietic stem cells (HSCs). Overall design: Flt3-negative, lineage-negative, Sca1+ and cKit+ cells (Flt3-LSKs) were sorted from bone marrow cells from control mice or those are deficient for Tcf1 and Lef1 transcription factors. Both genes were conditionally deleted using Vav-Cre
Publication Title
Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1.
Sample Metadata Fields
No sample metadata fields
View Samples