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Homo sapiens
40 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Although renal cell carcinoma (RCC) is the sixth-leading cause of cancer death, the molecular events leading to disease onset and progression are not well understood. Genomic profiling of clear cell RCC (cRCC) patients indicated that loss of a negative regulator of the Wnt pathway, secreted frizzled-related protein 1 (sFRP1), occurred in the majority of more than 100 patients tested. To our knowledge, this is the first report of loss of sFRP1 expression in patients diagnosed with cRCC; this loss occurs in early stage cRCC, suggesting that it may be an important early event in renal carcinogenesis. Genomic profiling of patient matched normal and cRCC tissues identified Wnt regulated genes to be aberrantly increased in cRCC tissues suggesting sFRP1 suppresses Wnt signaling in cRCC. In order to test the hypothesis that sFRP1 acts as a tumor suppressor in cRCC, we have stably expressed sFRP1 in cRCC cells. sFRP1 expression in cRCC cells resulted in decreased growth in cell culture, inhibition of anchorage-independent growth, and decreased tumor volume in a nude mouse model. Together these data suggest an important role for sFRP1 as a tumor suppressor in cRCC.
Publication Title
Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4g, Creb3l3 and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus-specific patterns for the transcription factor Gata3 and the secreted protein nephrocan.
Publication Title
Dynamic patterning at the pylorus: formation of an epithelial intestine-stomach boundary in late fetal life.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
We used microarrays to detail the program of gene expression underlying the growth of the plantaris muscle following synergist ablation-induced supraphysiological overload
Publication Title
Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
Background: The muscularis externa (ME) of the adult intestine consists of two layers of visceral smooth muscle (VISM), the inner circular muscle (ICM) and outer longitudinal muscle (OLM), that form sequentially beginning at embryonic day (E) 13 and E15 in the developing mouse. Coordinated contraction of these two layers facilitates the movement of food down the digestive tract. Though abnormal ME function or development has been linked to pseudoobstruction and irritable bowel syndrome, little is known about the molecular character of the smooth muscle that comprises this tissue. We performed transcriptome analysis to identify genes that are enriched in intestinal mesenchyme tissue at E14.5, when the inner circular muscle (ICM) is well established. Results: Expression patterns of enriched mesenchyme genes were examined in publically available in situ databases, revealing over one hundred genes that are expressed in the ICM. Examination of the promoter regions for these genes revealed enrichment for cJUN transcription factor binding sites and cJUN itself was also enriched in ICM. A cJUN ChIP-seq at E14.5 showed that cJUN regulatory regions contained characteristics of muscle enhancers. Overall design: E14.5 mouse intestines were harvested and grown for 24 hours in a transwell culture with or without Cyclopamine treatment. Separated epithelial and mesenchyme tissue populations or whole intestines were submitted for sequencing. Three replicates for each condition were collected.
Publication Title
Transcriptome of the inner circular smooth muscle of the developing mouse intestine: Evidence for regulation of visceral smooth muscle genes by the hedgehog target gene, cJun.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During organogenesis of the intestine, reciprocal crosstalk between the endodermally-derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation. Though both of these tissue layers participate in patterning, the mesenchyme is thought to play a prominant role in the determination of epithelial phenotype during development and in adult life. However, the molecular basis of this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in separated mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional crosstalk. We also catalog the most highly enriched transcription factors in both compartments and find evidence for a major role for Hnf4alpha and Hnf4 gamma in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue-restricted in their expression, mesenchymally-enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely non-tissue specific.
Publication Title
Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme.
Publication Title
Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Tendon is a hypocellular tissue that contains functional cable-like units of type I collagen responsible for the transmission of force from muscle to bone. In the setting of injury or disease, patients can develop chronic tendinopathies that are characterized by pain, loss of function and persistent inflammatory changes that are often difficult to treat. Platelet-rich plasma (PRP) has shown promise in the treatment of chronic tendinopathy, but little is known about the mechanisms by which PRP can improve tendon healing. PRP contains many different growth factors and cytokines, and since these proteins can both activate and inhibit various signaling pathways it has been challenging to determine precisely which signaling pathways and cellular responses are most important. Using state-of-the-art bioinformatics tools and genome wide-expression profiling, the purpose of this study was to determine the signaling pathways activated within cultured tendon fibroblasts in response to PRP treatment.
Publication Title
Platelet-Rich Plasma Activates Proinflammatory Signaling Pathways and Induces Oxidative Stress in Tendon Fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Xenopus laevis
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones.
Publication Title
Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.
Sample Metadata Fields
Specimen part
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SRP131305- Rattus norvegicus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis. Overall design: Rats were subjected to a bilateral full-thickness supraspinatus tear and suprascapular neurectomy. Samples (N=4 per group) were taken at 0 days (unoperated controls), 10 days, 30 days, and 60 days post-injury
Publication Title
Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated microRNA and mRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by miR-146-5p.
Sample Metadata Fields
Sex, Age, Specimen part
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