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GSE45234
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Publication Title
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Intact living conduit vessels (umbilical veins) were exposed to normal or high intraluminal pressure, or low or high shear stress in combination with a physiological level of the other force. We used a unique vascular ex vivo perfusion system. After six hours of perfusion endothelial cells were isolated from the stimulated vessels and RNA was extracted. RNA from 16 experiments from each stimulation were pooled and analyzed in duplicate DNA microarrays.
Publication Title
Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte cytoskeleton. To elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury. Upon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involving cytoskeletal-associated pathways, adhesion, migration and extracellular matrix composition to be affected. Everolimus is capable of protecting podocytes from injury, both on the transcriptome and protein level. Rescued genes included TUBB2B and DCDC2, both involved in microtubule structure formation in neuronal cells but not identified in podocytes so far. Confirming gene expression data, Western-blot analysis in cultured podocytes showed an increase of TUBB2B and DCDC2 protein after everolimus treatment, and immunohistochemistry in healthy control kidneys confirmed a podocyte-specific expression. Microtubule-inhibitor experiments led to a maldistribution of TUBB2B and DCDC2 as well as an aberrant reorganization of the actin cytoskeleton. Tubb2bbrdp/brdp mice showed a delay in glomerular podocyte and capillary development. Taken together, our study suggests that off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development
Publication Title
Everolimus Stabilizes Podocyte Microtubules via Enhancing TUBB2B and DCDC2 Expression.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
In this study, we set out to identify those molecular features of the POU transcription factor Oct4 that are responsible for inducing pluripotency in somatic cells. Oct4 is known to have a strong preference to cooperate with Sox2 on heterodimeric SoxOct elements predominantly found in enhancers of genes expressed in embryonic stem cells (ESCs). To test whether this partnership is specific to Oct4, we compared its DNA recognition and reprogramming activities to the paralogous transcription factor Oct6, which cannot induce and maintain pluripotency in mouse cells. By analyzing ChIP-Seq data and performing quantitative dimerization assays, we found that in somatic cells, instead of heterodimerzing with Sox-factors, Oct6 more potently homodimerizes on OctOct elements. We identified that a single amino acid is crucial in directing binding to the respective composite DNA element. As a consequence, just changing this one amino acid hampers Oct4 in generating induced pluripotent stem cells (iPSCs). In contrast, the reverse mutation in Oct6 did not augment its reprogramming activity. This was achieved with at least two additional exchanges. In summary, we demonstrate that cell-type specific POU factor function is determined by a limited set of residues that affect DNA and partner factor interactions. Such relatively minor changes lead to a pronounced impact on regulatory function and reprogramming activity.
Publication Title
Changing POU dimerization preferences converts Oct6 into a pluripotency inducer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p
Publication Title
miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.
Sample Metadata Fields
Subject
View Samples- Glycine max
- 2522 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
To identify soybean genes and QTLs associated with quantitative resistance to infection by the oomycete pathogen Phytophthora sojae, we conducted a very large-scale microarray experiment using 2522 Affymetrix GeneChips. The experiment involved assaying a total of 298 soybean recombinant inbred lines together with internal checks.
Publication Title
Infection and genotype remodel the entire soybean transcriptome.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP, we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP.
Publication Title
MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaHiSeq2500
Description
How cells acquire their fate is a fundamental question in both developmental and regenerative biology. Multipotent progenitors undergo gradual cell fate restriction in response to temporal and positional cues from the microenvironment, the nature of which is far from being clear. In the case of the lymphatic system, venous endothelial cells are thought to give rise to lymphatic vessels, through a process of trans-differentiation. Upon expression of a set of transcription factors, venous cells acquire a lymphatic fate, and bud out to generate the lymphatic vasculature. In this work we challenge this view and show that while lymphatic endothelial cells (LECs) do arise in the Cardinal Vein (CV), they do so from a previously uncharacterized pool of multipotent angioblasts. Using lymphatic-specific transgenic zebrafish, in combination with endothelial photoconvertible reporters, and long-term live imaging, we demonstrate that these multipotent angioblasts can generate not only lymphatic, but also arterious, and venous fates. We further reveal that the underlying endoderm serves as a source of Wnt5b, which acts as a lymphatic inductive signal, promoting the angioblast-to-lymphatic transition. Moreover, Wnt5b induced lymphatic specification in human embryonic stem cells- derived vascular progenitors, suggesting that this process is evolutionary conserved. Our results uncover a novel mechanism of lymphatic vessel formation, whereby multipotent angioblasts and not venous endothelial cells give rise to the lymphatic endothelium, and provide the first characterization of their inductive niche. More broadly, our findings highlight the CV as a plastic and heterogeneous structure containing different cell populations, analogous to the hematopoietic niche in the aortic floor. Overall design: Following Kaede photoconversion of dorsal or ventral halves of the PCV in Tg(fli1:gal4;uasKaede) embryos at 24 hpf, 6Â embryos per group were used for FACS isolation of Kaede photconverted (red) ECs.
Publication Title
Lymphatic vessels arise from specialized angioblasts within a venous niche.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcription can be quite disruptive for chromatin so cells have evolved mechanisms to preserve chromatin integrity during transcription, hence preventing the emergence of cryptic transcript from spurious promoter sequences. How these transcripts are regulated and processed by cells remains poorly characterized. Notably, very little is known about the termination of cryptic transcription. Here we used RNA-Seq to identify and characterize cryptic transcripts in Spt6 mutant cells (spt6-1004) in Saccharomyces cerevisiae. We found polyadenylated cryptic transcripts running both sense and anti-sense relative to genes in this mutant. Cryptic promoters were enriched for TATA boxes, suggesting that the underlying DNA sequence defines the location of cryptic promoters. While intragenic sense cryptic transcripts terminate at the terminator of the genes that host them, we found that anti-sense cryptic transcripts preferentially terminate at the 3’-end of upstream genes. These findings led us to demonstrate that most terminators in yeast are bidirectional, leading to termination and polyadenylation of transcripts coming from either direction. We propose that S. cerevisiae has evolved this mechanism in order to prevent spurious transcription from invading neighbouring genes, a feature particularly critical for organisms with small compact genomes. Overall design: Cells from spt16-1004 and its respective WT strain were grown to an OD600 of 0.5 at 30°C and shifted to 37°C for 80 min before RNA extraction. Total RNA was extracted using the hot phenol method. Prior to library preparation, total RNA was either depleted for ribosomal RNA using the Ribo-zero Gold yeast kit (Epicentre-Illumina) or enriched for polyadenylated RNA using the NEBnext Poly(A) kit (New England Biolabs). Strand specific RNA-seq libraries were prepared using the KAPA stranded RNA-Seq library preparation kit prior to paired-end sequencing on an Illumina Hi-Seq2000. Reads were mapped to the sacCer3 assembly of the S. cerevisiae genome using Tophat2 (23). Intron length range was set at 50 to 1000 bp and a reference annotation file was provided to guide the assembly.
Publication Title
Bidirectional terminators in Saccharomyces cerevisiae prevent cryptic transcription from invading neighboring genes.
Sample Metadata Fields
Cell line, Subject
View Samples