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GSE22306
Homo sapiens
22 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The two most common melanoma histopathologic subtypes, superficial spreading (SSM) and nodular melanoma (NM), are believed to represent sequential phases of linear progression from radial to vertical growth. Studies suggest, however, that SSM and NM are biologically distinct. We utilized an integrative genomic approach to examine the possibility that SSM and NM are the result of independent pathways characterized by unique molecular alterations. Cell lines including SSM, NM, metastatic melanoma, and melanocyte controls were evaluated for copy number changes and differential mRNA expression using single nucleotide polymorphism array (SNP 6.0, Affymetrix) and gene array (U133A 2.0, Affymetrix). Data sets were integrated to identify copy number alterations that correlated with gene expression, and array results were validated using immunohistochemistry on human tissue microarrays (TMAs) and an external data set. The functional effect of genomic deletion was assessed by lentiviral overexpression. Integrative genomics revealed 8 genes in which NM/SSM-specific copy number alterations were correlated with NM/SSM differential gene expression (P<0.05, Spearmans rank). Pathways analysis of differentially expressed genes (N=114) showed enrichment for metabolic-related processes. SSM-specific genomic deletions (DIS3, MTAP, G3BP2, SEC23IP, USO1) were verified in an expanded panel of cell lines, and forced overexpression of MTAP in SSM resulted in reduced cell growth. Metabolism-related gene ALDH7A1 was verified as overexpressed in NM using human TMAs.The identification of recurrent genomic deletions in SSM not present in NM challenges the linear model of melanoma progression and supports the unique molecular classification of SSM and NM.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Xenopus laevis
- 18 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Recently a new neonatal diabetes syndrome, Mitchell-Riley syndrome, was discovered. To identify the genetic cause of the syndrome homozygosity mapping was used, several chromosomal regions were linked to Mitchell-Riley syndrome. In situ hybridization of genes from one such region using model organism Xenopus laevis identified RFX6 as a potential candidate gene; mutant forms of RFX6 were subsequently found in Mitchell-Riley patients. Analysis of the expression pattern of RFX6 in Xenopus development shows it is expressed broadly in the endoderm early in development, and later RFX6 becomes restricted to the endocrine cells of the gut and pancreas. Morpholino knockdown of RFX6 in Xenopus caused a loss of pancreas marker gene expression. Injection of exogenous wild type RFX6 rescued the morpholino phenotype in Xenopus tadpoles. Attempts to rescue the loss-of-function phenotype using mutant forms of RFX6 found in Mitchell-Riley patients were unsuccessful suggesting the changes lead to loss-of-function and could be the cause of Mitchell-Riley syndrome. Microarray analysis of gene expression in knockdown tissue suggested a downregulation in marker genes for lung, stomach and heart, ambiguous results for the liver, and an upregulation in kidney marker gene expression. RT-PCR and in situ hybridization confirms a loss of lung, stomach and heart gene expression, no change in liver marker hex and an upregulation in kidney marker KcnJ1. The fact that the morpholino phenotype affects multiple organs suggests that RFX6 has a broad role early in endoderm development.
Publication Title
Functional analysis of Rfx6 and mutant variants associated with neonatal diabetes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina Mouse Ref-6 V1
Description
Systemic administration of -adrenoceptor (-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of -AR signaling has been highlighted by the inability of 13-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic acute administration of the 2-AR agonist formoterol. Skeletal muscle gene expression (from murine tibialis anterior) was profiled at both 1 and 4 hours following systemic administration of the 2-AR agonist formoterol, using 46K Illumina(R) Sentrix BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress.
Publication Title
Expression profiling of skeletal muscle following acute and chronic beta2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm.
Sample Metadata Fields
Treatment
View Samples- Xenopus laevis
- 4 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Epimorphic regeneration is the process by which complete regeneration of a complex structure such as a limb occurs through production of a proliferating blastema. This type of regeneration is rare among vertebrates but does occur in the African clawed frog Xenopus laevis, traditionally a model organism for the study of early development. Xenopus tadpoles can regenerate tails, limb buds and the lens of the eye, although the ability of the latter two organs to regenerate diminishes with advancing developmental stage. Using a heat shock inducible transgene that remains silent unless activated, we have established a stable line of transgenic Xenopus in which the BMP inhibitor Noggin can be over-expressed at any time during development. We have previously shown that activation of this transgene blocks regeneration of the tail and limb of Xenopus tadpoles. In the current study, we have taken advantage of this transgenic line to directly compare gene expression in same stage regenerating vs. non-regenerating hind limb buds. Using Affymetrix gene chip analysis, we have identified genes whose expression levels are linked to regenerative success. These include the BMP inhibitor Gremlin and the stress protein Hsp60 (no blastema in zebrafish). Analysis of overrepresented Gene Ontology functional groupings suggests that successful regeneration in the Xenopus hind limb depends on induction of stress response pathways. Furthermore, as expected, genes involved in embryonic development and growth are also significantly over-represented in regenerating early hind limb buds.
Publication Title
Identification of genes associated with regenerative success of Xenopus laevis hindlimbs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
A distinct highly invasive subpopulation was identified in breast cancer cell lines. The molecular characteristics of these cells was investigated, revealing a set of genes whose high expression confers the ability to invade.
Publication Title
ΔNp63α Promotes Breast Cancer Cell Motility through the Selective Activation of Components of the Epithelial-to-Mesenchymal Transition Program.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
MicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins, and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target of miR-29. In vitro radiolabeled acetate incorporation assays confirm that pharmacologic inhibition of miR-29 significantly reduces de novo cholesterol and fatty acid synthesis. Our findings indicate that miR-29 controls hepatic lipogenic programs, likely in part through regulation of Ahr and Sirt1, and therefore may represent a candidate therapeutic target for metabolic disorders such as dyslipidemia. Overall design: Hepatic mRNA profiles of C57BL/6J female mice treated with LNA against miR-29a, miR-29b and miR-29c versus saline.
Publication Title
Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer 'stemness' and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer 'stemness' and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Overall design: mRNA profiles of 4 normal omental MSCs and 10 ovarian CA-MSCs using Illumina TruSeq RNA Sample Preparation kit and Illumina HiSeq 100bp PE sequencing.
Publication Title
Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Using RNA sequencing (Illumina Hi-Seq 2000 sequencer) we report the transcriptome profile of primary human chondrocytes isolated from patients with hip osteoarthritis (OA), and the transcriptome response of these cells to 4h stimulation with IL-1ß (1ng/ml). In total, 983 long non-coding RNAs (lncRNAs) were identified, which included 642 intergenic lncRNAs (lincRNAs), 124 antisense and pseudogenes. Less than 4% of the identified lncRNAs overlapped with putative eRNAs regions, and visual inspection showed that they were uni-directional and multi-exonic. Upon IL-1ß stimulation 499 protein-coding genes were differentially expressed, and 158 lncRNAs were differentially expressed, including 92 lincRNAs, 13 antisense and 18 psudogenes. This study demonstrates that IL-1ß induces a rapid and widespread change in the transcriptome of the primary human OA chondrocyte. Overall design: RNA sequencing analysis of primary human chondrocytes isolated from n=3 patients with hip osteoarthritis, with and without 4h IL-1b (1ng/ml) stimulation
Publication Title
Long Intergenic Noncoding RNAs Mediate the Human Chondrocyte Inflammatory Response and Are Differentially Expressed in Osteoarthritis Cartilage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional coregulator TLE3 inhibits mitochondrial and metabolic gene expression in beige adipocytes. Overall design: mRNA profiles of iWAT immortalized preadipocytes, differentiated in culture, and knocking out TLE3 after differentiation, were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
Publication Title
Loss of TLE3 promotes the mitochondrial program in beige adipocytes and improves glucose metabolism.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples