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GSE27993
Homo sapiens
10 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to detect the differences in gene-expression of the periontal ligament between patients with healthy periodontal ligament and patients with periodontitis
Publication Title
The pathology of bone tissue during peri-implantitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study we want to ascertain the differences and similarities of infected and inflammated peri implant tissue versus healthy peri implant tissue at the mRNA level.
Publication Title
The pathology of bone tissue during peri-implantitis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents. In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents. Mice, bearing plasma cell tumors lived an average of 70 days longer on combination treatment compared to single agents. A set of 37 genes cooperatively affected (34 down-regulated; 3 up-regulated) by the combination responded pharmacodynamically in human myeloma cell lines, xenografts, and a P493 model, and were both enriched in tumors, and correlated with prognostic markers in myeloma patient datasets. Genes down-regulated by the combination were overexpressed in several untreated cancers (breast, lung, colon, sarcoma, head and neck, myeloma) compared to normal tissues. The MYC/E2F axis, identified by upstream regulator analyses and validated by immunoblots, was significantly inhibited by the drug combination in several myeloma cell lines. Furthermore, 88% of the 34 genes downregulated have MYC binding sites in their promoters, and the drug combination cooperatively reduced MYC half-life by 55% and increased degradation. Thus, integrative approaches to understand drug synergy identified a clinically actionable strategy to inhibit MYC/E2F activity and tumor cell growth in vivo.
Publication Title
Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 52 Downloadable Samples
Illumina HiSeq 2000
Description
Transcriptomics data obtained from limiting amounts of mRNA is often noisy, providing primarily qualitative changes in transcript expressions. So far, technical variations arising out of the library preparation protocols have not been adequately characterized at reduced levels of mRNA. Here, we generated sequencing libraries from limiting amounts of mRNA using three amplification-based methods, viz. Smart-seq, DP-seq and CEL-seq, and demonstrated significant technical variations in these libraries. Reduction in mRNA levels led to inefficient amplification of the majority of low to moderately expressed transcripts. Furthermore, stochasticity in primer hybridization and/or enzyme incorporation was magnified during the amplification step resulting in significant distortions in fold changes of the transcripts. Consequently, the majority of the differentially expressed transcripts identified were either high-expressed and/or exhibited high fold changes. High technical variations, which were sequencing depth independent, ultimately masked subtle biological differences mandating the development of improved amplification-based strategies for quantitative transcriptomics from limiting amounts of mRNA. Overall design: Sequencing libraries were prepared from serial dilutions of mRNA, ranging from 1 ng to 25 pg, using three amplification-based methods, viz. Smart-seq, DP-seq and CEL-seq. The mRNA was derived from an in vitro model of lineage segregation achieved by modulating TGF beta signaling pathway in differentiating mouse embryonic stem cells.
Publication Title
Technical variations in low-input RNA-seq methodologies.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Here we identify HOXA5 as an important repressor of intestinal stem cell fate in vivo and identify a reciprocal feedback between HOXA5 and Wnt signaling. HOXA5 is suppressed by the Wnt pathway to maintain stemness and becomes active only outside the intestinal crypt where it inhibits Wnt signaling to enforce differentiation. In colon cancer, HOXA5 is down-regulated and its re-expression induces loss of the cancer stem cell phenotype preventing tumor progression and metastasis. Tumor regression by HOXA5 induction can be triggered by retinoids, which represents a tangible means to treat colon cancer by eliminating cancer stem cells.
Publication Title
HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Zea mays
- 6 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
The maize inbred line A661 shows a characteristic phenotype when grown at suboptimal temperatures for three weeks and then is exposed to optimal temperatures for one extra week. After this period the third leaf showed two well defined sections: distal (chlorophyll-less; CL) and proximal (chlorophyll-containing; CC) sections. To further investigate the performance of the inbred line A661 under cold conditions a gene expression profiling analysis was conducted using large scale maize microarrays. A total of 1002 transcripts change their expression between both leaf sections and the majority of these codify for proteins located to the chloroplast.
Publication Title
Genetic regulation of cold-induced albinism in the maize inbred line A661.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
We used zebrafish embryos as an in vivo system to investigate the role of the microRNA-146 family (consisting of 2 members miR-146a and miR-146b) in the innate immune response to S. typhimurium infection. To determine the role of miR-146 microRNAs in the response to S. typhimurium infection we used Illumina RNA sequencing to compare the mRNA expression profiles of control embryos versus embryos with knockdown of miR-146a and miR-146b. RNA sequencing analysis of miR-146 knockdown embryos showed no major effects on pro-inflammatory gene expression or on the expression of transcriptional regulators and signal transduction components of the immune response. In contrast, apoliprotein-mediated lipid transport emerged as an infection-inducible pathway under miR-146 knockdown conditions, suggesting a function of miR-146 in regulating lipid metabolism during inflammation. Overall design: Embryos were injected at the one cell stage with a combination of two morpholinos targeting miR-146a and miR-146b, or with the standard control morpholino from GeneTools. Subsequently, at 28 hours post fertilzation (hpf) they were infected by injecting 200-250 colony forming units of S. typhimurium strain SL1027 into the caudal vein, or mock-injected with PBS. RNA was isolated at 8 hours post injection (hpi) for Illumina RNAseq analysis. Two independent experiments were performed for RNAseq analysis of biological duplicates.
Publication Title
MicroRNA-146 function in the innate immune transcriptome response of zebrafish embryos to Salmonella typhimurium infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.
Sample Metadata Fields
Specimen part
View Samples- Ovis aries
- 40 Downloadable Samples
- Ovine Gene 1.1 ST Array (ovigene11st)
Description
Feeding animals with either concentrates supplemented with vitamin E or alfalfa grazing has been proven to reduce the oxidative process that occurs in meat products. Indoor-kept lambs were fed a standard concentrate (n=7, C) or concentrate supplemented with vitamin E (n=7, VE) for 30 days before slaughtering all animals at 2224 kg of live weight. Simultaneously, 7 unweaned lambs grazed in alfalfa paddocks (ALF) with their dams. Global transcriptomic data of longissimus thoracis (LT) muscle and subcutaneous fat (SF) with the Affymetrix Ovine Gene 1.1 microarray was used. In LT muscle when ALF group was compared with C group, were identified 41 genes differentially expressed. Among these genes 32 were down- regulated and 9 were up- regulated. Meanwhile when VE treatment was compared with C group were identified a total of 29 genes, 26 were down- regulated and 3 genes were up- regulated. In SF when ALF treatment was compared with C, were identified only 4 genes differentially expressed, all of them up-regulated in ALF group. Meanwhile when VE treatment was compared with C group, were identified a total of 330 genes. Among them, 295 genes were up- regulated and 35 were down- regulated. In LT muscle the clusters corresponding to gene expression profiles from treatments ALF, C and VE were clearly separated from each other. In SF, ALF group, overlap with VE and C treatments, however, VE and C clearly were separate in different clusters. These differentially expressed genes were selected for a functional analysis by using DAVID. In LT muscle some of the identified significant biological processes were catabolic and lipid process (down-regulated, except CPT1B) (CPT1B, PLA2G16, SPSB1, LRTOMT, PLCD4, FBXO9, CNBP and CYP27A1) and muscle organ differentiation (down-regulated) (CPT1B, MYOD1, MYLK2 and MSTN) in ALF; whereas intracellular signaling cascade (IGF1R, DEF8, AKAP7 and CISH) was down-regulated. In SF, vitamin E supplementation had an important effect; most of the genes were up-regulated. DAVID analysis showed that biosynthesis lipid pathway was the most represented with 20 genes, such as EBP, MVD, CYP51A1, DHCR7, HMGCS1, LSS and FDFT1 implicated in cholesterol synthesis. Further exploration of the links between these genes and vitamin E will lead to a better understanding of how vitamin E affects the oxidative process that occurs in meat products.
Publication Title
Genome-wide expression profiling in muscle and subcutaneous fat of lambs in response to the intake of concentrate supplemented with vitamin E.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HiSeq 2000
Description
Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as central interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, peripheral interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.
Publication Title
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.
Sample Metadata Fields
Specimen part
View Samples