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SRP137825
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
We recently described TRIM8, a nuclear E3 ubiquitin ligase, whose expression inversely correlates with glioma grade. TRIM8 restoration suppresses cell growth and induces a significant reduction of clonogenic potential in both U87MG glioblastoma and patients' primary glioma cell lines. Since E3 ubiquitin ligase proteins regulate carcinogenesis through the timely control of many cellular processes such as DNA damage response, metabolism, transcription, and apoptosis, we reasoned that TRIM8 activity might impact on cell transcriptome patterns, thereby promoting cancer development and progression. Therefore, we profiled the whole transcriptome of normal embryonic neural stem cells (eNSC) infected with a retrovirus expressing FLAG-Trim8 by using RNA-Seq. RNA-Seq revealed 1365 differentially expressed transcripts of 912 genes. 723 of them (corresponding to 648 RefSeq genes) differed significantly of at least 1.5 folds (192 upregulated transcripts of 178 genes and 531 downregulated transcripts of 470 genes). 80 genes, among all differentially expressed genes, resulted to significantly enrich 18 pathways by IPA analysis. 53% of these genes (43 out of 80 genes) are related to cell-morphology, cell death and survival, with a preponderantly representation of signaling pathways related to neurotransmission and to CNS, including axonal guidance, GABA Receptor, ephrin B, synaptic long-term potentiation/depression, and glutamate receptor. Specifically, our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different pathways, including JAK-STAT. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3 with possible implications in the development and progression of glioma. Overall design: Profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells using RNA-Seq
Publication Title
TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 21 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.
Publication Title
Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established, little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals
Publication Title
Using transcription modules to identify expression clusters perturbed in Williams-Beuren syndrome.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA-Sequencing analysis of 18 papillary thyroid carcinoma biopsies and of 4 healthy donors'' thyroids. In this analysis we assessed differential gene expression and investigated the mutational landscape in this tumor type. Analysis of gene fusion was also performed, leading to the identification of a novel chimeric transcript, potential driver in tumor initiation. Overall design: Total RNA isolated from 18 papillary thyroid carcinoma biopsies and 4 healthy donors'' thyroids.
Publication Title
New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.
Publication Title
The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Lung cancer is a highly malignant tumor and the majority of cancer-related deaths are due to metastasis. The tumor microenvironment (TME) plays a fundamental role in the metastatic spread of tumor cells. Among other stromal cells, mesenchymal stem cells (MSCs) are known to be present within the TME and to be involved in cancer progression. However the majority of previous studies have been performed on bone marrow-derived MSCs. To investigate the role of the TME on the pulmonary MSC phenotype, we compared the expression profile of paired MSCs isolated from lung tumor (T-) and normal adjacent tissues (N-) from lung carcinoma patients.
Publication Title
Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Stress is a powerful modulator of neuroendocrine, behavioral and immunological functions. After 4.5 days of repeated combined acoustic and restraint stress as a murine model of chronic psychological stress severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turn-over, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice .Thus, in our murine model, repeated stress caused severe metabolic dysregulations leading to a drastic reduction of the individual's energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.
Publication Title
Hypermetabolic syndrome as a consequence of repeated psychological stress in mice.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Stress is a powerful modulator of neuroendocrine, behavioral and immunological functions. After 4.5 days of repeated combined acoustic and restraint stress as a murine model of chronic psychological stress severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turn-over, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice .Thus, in our murine model, repeated stress caused severe metabolic dysregulations leading to a drastic reduction of the individual's energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.
Publication Title
Hypermetabolic syndrome as a consequence of repeated psychological stress in mice.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Stress is a powerful modulator of neuroendocrine, behavioral and immunological functions. After 4.5 days of repeated combined acoustic and restraint stress as a murine model of chronic psychological stress severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turn-over, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice .Thus, in our murine model, repeated stress caused severe metabolic dysregulations leading to a drastic reduction of the individual's energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.
Publication Title
Hypermetabolic syndrome as a consequence of repeated psychological stress in mice.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We have previously demonstrated that bone marrow-derived DC can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes (T1D). The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules and secreted low levels of IL-12p70. The protective DC therapy induced regulatory Th2 cells that shifted the dominant Th1 environment, present in NOD mice, to a mixed Th1/Th2 milieu. Microarray analysis of therapeutic and non-therapeutic DC populations revealed several novel molecules that could play important roles in the observed DC-mediated therapy. The therapeutic DC population expressed a unique pattern of costimulatory molecules and chemokines, which were confirmed by flow cytometry and ELISA assays. We have performed in vitro chemotaxis assays that demonstrated the therapeutic DC preferentially attracted Th2 cells, as compared to Th1, Treg or nave T cells. In addition we quantified the in vivo migration of activated islet-specific T cells to the pancreas using novel cell labeling techniques and 19F nuclear magnetic resonance. A subcutaenous injection of therapeutic DC alters the migration of both Th1 and Th2 cells to the pancreas, and Th1 cells appeared in the lymph node draining the site of DC injection. These results suggest that the therapeutic function of DC is mediated in part by the chemoattractive properties of these DC for diabetogenic Th1 cells.
Publication Title
Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules.
Sample Metadata Fields
Sex
View Samples