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E-TABM-52
Arabidopsis thaliana
52 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Nine accessions of Arabidopsis were sampled before and after 14d of cold acclimation at 4°C. Transcript data were combined with metabolite data and related to quantitative measurement of plant freezing tolerance as determined by leaf electrolyte leakage assays.
Publication Title
Natural genetic variation of freezing tolerance in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways.
Publication Title
High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaHiSeq2000
Description
Epigenetic and metabolic reprogrammings are implicated in cancer progression with unclear mechanisms. We report here that the histone methyltransferase NSD2 drives cancer cell and tumor resistance to therapeutics such as tamoxifen, doxorubicin, and radiation by reprogramming of glucose metabolism. NSD2 coordinately up-regulates expression of TIGAR, HK2 and G6PD and stimulates pentose phosphate pathway (PPP) production of NADPH for ROS reduction. We discover that elevated expression of TIGAR, previously characterized as a fructose-2,6-bisphosphatase, is localized in the nuclei of resistant tumor cells where it stimulates NSD2 expression and global H3K36me2 mark. Mechanistically, TIGAR interacts with the antioxidant regulator Nrf2 and facilitates chromatin assembly of Nrf2-H3K4me3 methylase MLL1 and elongating Pol-II, independent of its metabolic enzymatic activity. In human tumors, high levels of NSD2 correlate strongly with early recurrence and poor survival and are associated with nuclear-localized TIGAR. This study defines a nuclear TIGAR-mediated, epigenetic autoregulatory loop functioning in redox rebalance for resistance to tumor therapeutics. Overall design: A total of 4 samples were analyzed in this study. The study included two cell lines, MCF7 and the tamoxifen-resistant subline TMR. Both were were cultured in medium containing vehicle control and/or 4-hydroxytamoxifen (Tam). The untreated MCF7 and TMR cell lines served as controls for the study.
Publication Title
Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Transcriptomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout: Egln3, a negative regulator of NF-FB, was shown to be a direct miR-31 target; miR-31 inhibition/deletion resulted in suppression of miR-31-associated-EGLN3-NF-KB controlled inflammatory pathways.
Publication Title
Abrogation of esophageal carcinoma development in miR-31 knockout rats.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Microarray gene expression profiling reveals that PHGDH inhibition by NCT-503 activates a metabolic stress response characterized by downregulation of cell cycle genes and induction of stress response genes.
Publication Title
Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- 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- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Canonical IKK/NF-B signaling is a master regulator of inflammation and innate immunity and has been implicated in the pathogenesis of T1D. To investigate the impact of NF-B activation on -cell homeostasis and diabetes development, we generated a transgenic gain-of-function mouse model allowing conditional NF-B activation via expression of IKK2-CA (constitutively active IKK2 allele) in -cells using the tetracycline-regulated gene expression system. Pdx-1-tTA (knockin model generating Pdx-1 haploinsufficiency) driver mice were used for -cell specific transgene expression. Double transgenic IKK2-CA-pdx-1 mice develop a full-blown immune-mediated diabetes.To identify gene expression changes underlying this diabetes development pancreatic islets of diabetic IKK2-CA-Pdx-1, PDX-1 +/- and control mice were prepared and isolated total RNA was used for microarray analysis.
Publication Title
Long-term IKK2/NF-κB signaling in pancreatic β-cells induces immune-mediated diabetes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The MYC oncogene, which is commonly mutated/amplified in tumors, represents an important regulator of cell growth owing to its ability to induce both proliferation and apoptosis. Recent evidence links MYC to altered miRNA expression, thereby suggesting that MYC-regulated miRNAs might contribute to tumorigenesis. To further analyze the impact of MYC-regulated miRNAs we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system in order to control its expression. Microarray-based miRNA expression profiling revealed both known and novel MYC targets. Among the miRNAs repressed by MYC we identified the potential tumor suppressor miR-26a, which possessed the ability to attenuate proliferation in MYC-dependent cells. Interestingly, miR-26a was also found to be deregulated in primary human Burkitt lymphoma samples, thereby likely being of clinical relevance. While today only few miRNA targets have been identified in human disease, we could show that ectopic expression of miR-26a influenced cell cycle progression by targeting the bona fide oncogene EZH2, a Polycomb protein and global regulator of gene expression yet unknown to be regulated by miRNAs. Thus, in addition to directly targeting protein-coding genes, MYC modulates genes important to oncogenesis via deregulation of miRNAs, thereby vitally contributing to MYC-induced lymphomagenesis.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Glioblastoma cells are characterized by a highly invasive behavior whose mechanisms are not yet understood. Using the wound healing and Boyden chamber assays we compared in the present study the migration and invasion abilities of 5 glioblastoma cell lines (DK-MG, GaMG, U87-MG, U373-MG, SNB19) differing in p53 and PTEN status. We also analyzed by Western blotting the expression of PTEN, p53, mTOR and several other marker proteins involved in cell adhesion, migration and invasion. Among 5 cell lines, GaMG cells exhibited the fastest rate of wound closure, whereas U87-MG cells showed the most rapid chemotactic migration in the Boyden chamber assay. In DK-MG and GaMG cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG, U373-MG and SNB19 cells preferentially expressed F-actin in filopodia and lamellipodia. Moreover, the two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) were found to exhibit the fastest invasion rates through the Matrigel matrix.
Publication Title
Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status.
Sample Metadata Fields
Specimen part, Cell line
View Samples