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GSE45292
Caenorhabditis elegans
4 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
We have discovered rifampicin as a glycation inhibitor, which increases life span in C elegans. In order to understand the mechanism of rifampicin action, microarray analysis was performed to study the changes in gene expression brought about by the drug.
Publication Title
Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We investigated gene expression signatures in subcutaneous adipose tissue obtained from control subjects, premanifest HD gene carriers and manifest HD subjects with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD.
Publication Title
Analysis of White Adipose Tissue Gene Expression Reveals CREB1 Pathway Altered in Huntington's Disease.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared to controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV et al. (2005) Proc Natl Acad Sci U S A 102: 11023-11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies.
Publication Title
Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
Illumina HiSeq 2500
Description
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. Overall design: Expression profiling by high throughput sequencing data; GPL17021 Illumina HiSeq 2500 (Mus musculus)
Publication Title
Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DC), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished LXR-dependent induction of DC chemotaxis. Using the LDLR-/- mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for efficient emigration of DCs in response to chemotactic signals during inflammation.
Publication Title
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse BMDCs were differentiated from bone marrow by GM-CSF and IL-4 for 9 days.
Publication Title
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 77 Downloadable Samples
- Illumina HiSeq 2000
Description
Huntington's disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Transcriptional profiling of muscle in treated and untreated wild-type and R6/2 mice was performed to analyze the effect of the ActRIIB decoy on genes and pathways involved in maintaining normal muscle physiology as well as those dysregulated due to the mutant HTT gene mutation. Overall design: RNAseq was performed on tibialis muscle from wild-type, wildtype + decoy, R6/2 and R6/2 + decoy; N = 10 per group. RNAseq was done on an Illumina Hi-seq 2000. Paired-end sequencing was obtained, 4-plexed across lanes for a minimum of 38 million 50mer paired reads per sample
Publication Title
Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington's disease mice.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples- Escherichia coli
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
As part of our studies on the biological functions of polyamines we have used a mutant of Escherichia coli that lacks all the genes for polyamine biosynthesis for a global transcription analysis on the effect of added polyamines. The most striking early response to polyamine addition is the increased expression of the genes for the glutamate dependent acid resistance system (GDAR) that is essential for the survival of bacteria when passing through the acid environment of the stomach. Not only were the two genes for glutamate decarboxylases (gadA and gadB) and the gene for glutamate --aminobutyrate antiporter (gadC) induced by polyamine addition, but also the various genes involved in the regulation of this system were induced. We confirmed the importance of polyamines for the induction of the GDAR system by direct measurement of glutamate decarboxylase activity and acid-survival. Effects of deletions of the regulatory genes in the GDAR system and on the effects of overproduction of two of these genes were also studied. Strikingly, overproductions of the alternate sigma factor rpoS and of the regulatory gene gadE resulted in very high levels of glutamate decarboxylase and almost complete protection against acid stress even in the absence of any polyamines. Thus, these data show that a major function of polyamines in E. coli is protection against acid stress by increasing the synthesis of glutamate decarboxylase, presumably by increasing the levels of the rpoS and gadE regulators.
Publication Title
Polyamines are critical for the induction of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli.
Sample Metadata Fields
Treatment
View Samples- Escherichia coli
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Glutathionylspermdine synthetase/amidase (Gss) and the encoding gene (gss) have only been described in two widely separated species; namely Escherichia coli and several members of the Kinetoplastida phyla. In the present paper we have studied the species distribution more extensively. It is striking that all of the 75 Enterobacteria species that has been sequenced contain sequences with very high degree of homology to the E. coli Gss protein. Although homologous sequences are also present in various other bacteria, in contrast to Enterobacteria they are not present in all species of a given phyla. As previously reported homologous sequences were found in all five species of Kinetoplastids tested (including Trypansosma cruzi), but it is striking that comparable sequences are not found in a variety of invertebrate and vertebrate species, Archea and plants. Studies in E. coli show that the highest accumulation of glutathionylspermidine is found in stationary phase cultures where most of the intracellular spermidine is converted to glutathionylspermidine. However, even in log phase cells there is some formation of glutathionylspermidine, and isotope exchange experiments show that there is a rapid exchange between glutathionylspermidine and intracellular spermidine. We have not been able to define a specific physiologic function for glutathionylspermidine, but microarray studies comparing gss+ and -gss strains of E. coli show that a large number of genes are either upregulated or downregulated by the loss of the gss gene.
Publication Title
Escherichia coli glutathionylspermidine synthetase/amidase: phylogeny and effect on regulation of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA (siRNA) targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-kappaB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD. We found that both DAP12 knockdown and control clones were capable of equally responding to phorbol 12-myristate 13-acetate (PMA), a known inducer of morphological differentiation of THP-1 cells, by exhibiting almost similar gene expression profiles between both, following a 24-hour exposure to 50 nM PMA.
Publication Title
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease.
Sample Metadata Fields
Specimen part
View Samples