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SRP173793
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
High grade serous carcinoma (HGSC) arising from either the fallopian tube or ovary has a poor prognosis primarily due to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer (OvCa)1,2, but a systematic examination of both the tumor and stromal compartments is critical to understanding OvCa metastasis. We developed a label-free proteomic workflow to analyze as few as 5,000 formalin-fixed, paraffin embedded cells microdissected from each compartment. The tumor proteome was comparatively stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and the proteins it regulates. Stromal NNMT expression was necessary and sufficient for several functional aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT supported OvCa migration, proliferation, and in vivo growth and metastasis. Expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with extensive gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma and a novel treatment target. Overall design: Three biological replicates of normal murine 3T3 fibroblasts expressing either control or NNMT overexpression construct were grown for 48 hours in physiological levels of methionine before RNA was collected and sequenced to identify genes differentially regulated in response to NNMT.
Publication Title
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.
Sample Metadata Fields
Cell line, Subject
View Samples- Populus x canadensis, Populus maximowiczii x populus nigra
- 24 Downloadable Samples
Affymetrix Poplar Genome Array (poplar)
Description
As exposure to episodic drought can impinge significantly on forest health and the establishment of productive tree plantations, there is great interest in understanding the mechanisms of drought response in trees. The ecologically dominant and economically important genus Populus, with its sequenced genome, provides an ideal opportunity to examine transcriptome level changes in trees in response to a drought stimulus. The transcriptome level drought response of two commercially important hybrid Populus clones (P. deltoides P. nigra, DN34, and P. nigra P. maximowiczii, NM6) was characterized over a diurnal period using a 4 2 2 completely randomized factorial ANOVA experimental design (four time points, two genotypes, and two treatment conditions) using Affymetrix Poplar GeneChip microarrays. Notably, the specific genes that exhibited changes in transcript abundance in response to drought differed between the genotypes and/or the time of day that they exhibited their greatest differences. This study emphasizes the fact that it is not possible to draw simple, generalized conclusions about the drought response of the genus Populus on the basis of one species, nor on the basis of results collected at a single time point. The data derived from our studies provide insights into the variety of genetic mechanisms underpinning the Populus drought response, and provide candidates for future experiments aimed at understanding this response across this economically and ecologically important genus.
Publication Title
Genotype and time of day shape the Populus drought response.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To screen for specific circadian outputs that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared to that found in the rat SCN in vivo and SCN2.2 cells in vitro. Similar to the scope of circadian gene expression in SCN2.2 cells and the rat SCN, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Bmal1 (Mop3), and Cry1 and 323 functionally diverse transcripts (2.6%), many of which were involved in cell communication. Overlap in rhythmically-expressed transcripts among NIH/3T3 fibroblasts, SCN2.2 cells and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared to NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among cellular pathways mediating glucose metabolism and neurotransmission. Coupled with evidence for the rhythmic regulation of the inducible isoform of nitric oxide synthase, the enzyme responsible for the production of nitric oxide, in SCN2.2 cells and the rat SCN but not in fibroblasts, studies examining the effects of a NOS inhibitor on metabolic rhythms in co-cultures containing SCN2.2 cells and untreated NIH/3T3 cells suggest that this gaseous neurotransmitter may play a key role in SCN pacemaker function. Thus, this comparative analysis of circadian gene expression in SCN and non-SCN cells may have important implications in the selective identification of circadian signals involved in the coupling of SCN oscillators and the regulation of rhythmicity in downstream cells or tissues.
Publication Title
Circadian profiling of the transcriptome in NIH/3T3 fibroblasts: comparison with rhythmic gene expression in SCN2.2 cells and the rat SCN.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The capacity of embryonic stem cells to differentiate into all lineages of mature organism is precisely regulated by cellular signaling factors. STAT3 is a crucial transcription factor that plays a central role in maintaining embryonic stem cells identity. However the underlying mechanism how Stat3 directs differentiation is still not completely understood. Here we show that Stat3 positively regulates gene expression of methyltransferase like protein 8 (Mettl8) in mouse ES cells. We found that Mettl8 is dispensable for pluripotency but affects ESCs differentiation. Subsequently we discovered that Mettl8 interacts with Mapkbp1's mRNA, which is an intermediate factor in JNK signaling, and inhibits the translation of the mRNA. Thereby, Mettl8 prohibits the activation of JNK signaling and enhances the differentiation of mouse ESCs. Collectively, our study uncovers a Stat3 target Mettl8 which regulates mouse ESCs differentiation via JNK signaling. Overall design: mRNA profiles of E14 cells transfected with scramble siRNA or Mettl8 siRNA were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
The STAT3 Target Mettl8 Regulates Mouse ESC Differentiation via Inhibiting the JNK Pathway.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The use of radiation treatment has increased for both sporadic and neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS). However, there are a subset of radioresistant tumors and systemic treatments that are seldom used in these patients. We investigated molecular alterations after radiation in three NF2-associated and five sporadically operated recurrent VS after primary irradiation. We compared these findings with 49 non-irradiated (36 sporadic and 13 NF2-associated) VS through gene-expression profiling and pathway analysis. Furthermore, we stained the key molecules of the distinct pathway by immunohistochemistry. A total of 195 differentially expressed genes in sporadic and NF2-related comparisons showed significant differences based on the criteria of p value < 0.05 and a two-fold change. These genes were involved in pathways that are known to be altered upon irradiation (e.g., mammalian target of rapamycin (mTOR), phosphatase and tensin homolog (PTEN) and vascular endothelial growth factor (VEGF) signaling). We observed a combined downregulation of PTEN signaling and an upregulation of mTOR signaling in progressive NF2-associated VS after irradiation. Immunostainings with mTOR and PTEN antibodies confirmed the respective molecular alterations. Taken together, mTOR inhibition might be a promising therapeutic strategy in NF2-associated VS progress after irradiation.
Publication Title
Contribution of mTOR and PTEN to Radioresistance in Sporadic and NF2-Associated Vestibular Schwannomas: A Microarray and Pathway Analysis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
screening of AtMYB44-responsive genes under 250mM NaCl treatment
Publication Title
Overexpression of AtMYB44 enhances stomatal closure to confer abiotic stress tolerance in transgenic Arabidopsis.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Vascular smooth muscle cells (VSMCs) respond to biomechanical stretch with specific changes in gene expression which govern the phenotype of these cells. The mechanotransducer zyxin is a
Publication Title
Loss of the mechanotransducer zyxin promotes a synthetic phenotype of vascular smooth muscle cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Multiple Myeloma (MM) is a plasma cell tumor localized to the bone marrow (BM). Despite current progress in improving patient outcome, MM remains largely incurable. Disease clonal and interpatient heterogeneity has hampered identification of a common underlying mechanism for disease establishment and have slowed the development of novel targeted therapies. Epigenetic aberrations are now emerging as increasingly important in tumorigenesis, thus selective targeting of crucial epigenetic enzymes may provide new therapeutic potential in cancer including MM. Recently, we and others suggested the histone methyltransferase enhancer of zeste homolog 2 (EZH2), to be a potential therapeutic target in MM. Now we show that pharmacological inhibition of EZH2 suppresses the MM cell growth through downregulation of MM-associated oncogenes; IRF-4, XBP-1, PRDM1/BLIMP-1and c-MYC. We also show that downregulation of these genes is mediated via reactivated expression of microRNAs with tumor suppressor functions; primarily miR125a-3p and miR320c. Using chromatin immunoprecipitation (ChIP) we demonstrate that miR125a-3p and miR320c are targets of EZH2 and H3K27me3 in MM cell lines and primary MM cells. Our results further highlight the importance of polycomb-mediated silencing in MM to include microRNAs with tumor suppressor activity. This novel role further strengthens the oncogenic features of EZH2 and its potential as a therapeutic target in MM.
Publication Title
EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
V600E being the most common mutation in BRAF, leads to constitutive activation of the MAPK signaling pathway. The majority of V600E BRAF positive melanoma patients treated with the BRAF inhibitor vemurafenib showed initial good clinical responses but relapsed due to acquired resistance to the drug. The aim of the present study was to identify possible biomarkers associated with the emergence of drug resistant melanoma cells. To this end we analyzed the differential gene expression of vemurafenib-sensitive and vemurafenib resistant brain and lung metastasizing melanoma cells.
Publication Title
Vemurafenib resistance selects for highly malignant brain and lung-metastasizing melanoma cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples