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GSE9447
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced 2-6-sialylation on N-glycans, resulting from over-expression of the Golgi enzyme -galactoside:2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Sia2-3Gal1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on 1-integrins enhanced their binding to ligands, and stimulated cell motility. Here we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for an MMTV-promoter-driven polyoma-middle-T antigen, a tumor in which beta1-integrin function is important for tumorigenesis, and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1 null animals were more differentiated in comparison to those in the wild-type background, both by histological analysis and by protein expression profiles. Furthermore, we show the St6gal1 null tumors have selectively altered expression of genes associated with focal adhesion signaling, and have decreased phosphorylation of FAK, a downstream target of 1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced 1-integrin function.
Publication Title
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 129 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 129 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. Trait-associated SNPs located in putative regulatory regions likely exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. To this end, left ventricular mycardium samples from non-diseased human donor hearts were hybridized to Illumina HumanOmniExpress BeadChips for genotyping (n = 129) and Illumina Human HT12 Version 4 BeadChips (n = 129) for transcription profiling.
Publication Title
Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neuronal, endocrine and exocrine cells exhibit regulated exocytosis but there is also a body of evidence for regulated exocytosis from other cell types. Myofibroblasts are a stromal cell type that secretes extracellular matrix proteins, growth factors and cytokines; they are important in wound healing and increasingly are recognised to play a role in modifying the cellular microenvironment in cancer. We have established calcium dependent regulated secretion in a subset of myofibroblasts from gastric cancers, adjacent tissue and from normal tissue. We have used microarrays to look for the expression of genes associated with the regulated secretory phenotype.
Publication Title
The neuroendocrine phenotype of gastric myofibroblasts and its loss with cancer progression.
Sample Metadata Fields
Specimen part
View Samples- Hordeum vulgare
- 35 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Drought tolerance is a key trait for increasing and stabilizing barley productivity in dry areas worldwide. Identification of the genes responsible for drought tolerance in barley (Hordeum vulgare L.) will facilitate understanding of the molecular mechanisms of drought tolerance, and also genetic improvement of barley through marker-assisted selection or gene transformation. To monitor the changes in gene expression at transcription levels in barley leaves during the reproductive stage under drought conditions, the 22K Affymetrix Barley 1 microarray was used to screen two drought-tolerant barley genotypes, Martin and Hordeum spontaneum 41-1 (HS41-1), and one drought-sensitive genotype Moroc9-75. Seventeen genes were expressed exclusively in the two drought-tolerant genotypes under drought stress, and their encoded proteins may play significant roles in enhancing drought tolerance through controlling stomatal closure via carbon metabolism (NADP malic enzyme (NADP-ME) and pyruvate dehydrogenase (PDH), synthesizing the osmoprotectant glycine-betaine (C-4 sterol methyl oxidase (CSMO), generating protectants against reactive-oxygen-species scavenging (aldehyde dehydrogenase (ALDH), ascorbate-dependant oxidoreductase (ADOR), and stabilizing membranes and proteins (heat-shock protein 17.8 (HSP17.8) and dehydrin 3 (DHN3). Moreover, 17 genes were abundantly expressed in Martin and HS41-1 compared with Moroc9-75 under both drought and control conditions. These genes were likely constitutively expressed in drought-tolerant genotypes. Among them, 7 known annotated genes might enhance drought tolerance through signaling (such as calcium-dependent protein kinase (CDPK) and membrane steroid binding protein (MSBP), anti-senescence (G2 pea dark accumulated protein GDA2) and detoxification (glutathione S-transferase (GST) pathways. In addition, 18 genes, including those encoding l-pyrroline-5-carboxylate synthetase (P5CS), protein phosphatase 2C-like protein (PP2C) and several chaperones, were differentially expressed in all genotypes under drought; thus, they were more likely general drought-responsive genes in barley. These results could provide new insights into further understanding of drought-tolerance mechanisms in barley.
Publication Title
Differentially expressed genes between drought-tolerant and drought-sensitive barley genotypes in response to drought stress during the reproductive stage.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Myelofibrosis (MF) is caused by genetic abnormalities involving the thrombopoietin (TPO)/MPL/JAK2 axis. Furthermore MF patients have elevated serum TPO levels. MF is also associated with reduced GATA1 content in MK suggesting that this abnormality represents a phenotypic modifier. In 2014, Dr. Crispino suggested that in MF abnormal TPO signaling induces a ribosomal deficiency hampering GATA1 mRNA translation in MK. Support for MK GATA1 deficiency as phenotypic modifier in MF was provided by the observation that mice carrying the Gata1low mutation reducing Gata1 transcription in MK develop myelofibrosis. Since reduced RBC half-life subject these mice to continuous erythroid stress, we investigated the TPO/Mpl axis in this model. In Gata1low and wild-type mice, TPO mRNA was expressed by bone marrow (BM), spleen and liver. The greatest expression (by 300-fold) was detected in liver. Gata1low livers expressed TPO mRNA levels 6-fold greater than wild-type livers. TPO protein was detected in BM, spleen, liver and peritoneum washes and plasma. The greatest levels where detected in plasma. Gata1low plasma contained TPO levels 2-fold lower than wild-type plasma, but 2-times greater than plasma from bleed wild-type mice and Mplnull mice with similar thrombocytopenia, suggesting that TPO is overproduced in Gata1low mice. JAK2 and STAT5 were easily detected in Gata1low BM bur barely detectable in wild-type BM, suggesting that in the former MPL is prompt to signaling activation. Furthermore, Gata1low LSK expressed levels of Mpl mRNA 3-times greater than wild-type cells but expressed cell-surface levels of MPL 2-times lower than wild-type cells and similar to those on LSK from TPO-treated wild-type mice, suggesting that MPL is down-modulated in Gata1low LSK. The Crispinos hypothesis that in MF activation of TPO/MPL/JAK2 induces a ribosomal deficiency hampering GATA1 mRNA translation and the realization that this axis is activated in Gata1low mice made us question the original hypothesis that reduced content of GATA1 in Gata1low MK results from deletion of lineage-specific enhancers. Microarray analyses indeed identified that Gata1low BM express a discordant ribosome signature including reduced expression of RPS24 and RPS36A, two genes mutated in Diamond Blackfan Anemia, a disease characterized by inefficient GATA1 mRNA translation. Electron microscopy identified that the cytoplasm of Gata1low MK contained poorly developed endoplasmic reticulum with rare polysomes. In conclusion, these results validate the Gata1low model as a MF model by indicating that these mice express an activated TPO/MPL axis and an abnormal ribosomal signature which may reduce efficiency of Gata1 mRNA translation.
Publication Title
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Myelofibrosis (MF) is caused by genetic abnormalities involving the thrombopoietin (TPO)/MPL/JAK2 axis. Furthermore MF patients have elevated serum TPO levels. MF is also associated with reduced GATA1 content in MK suggesting that this abnormality represents a phenotypic modifier. In 2014, Dr. Crispino suggested that in MF abnormal TPO signaling induces a ribosomal deficiency hampering GATA1 mRNA translation in MK. Support for MK GATA1 deficiency as phenotypic modifier in MF was provided by the observation that mice carrying the Gata1low mutation reducing Gata1 transcription in MK develop myelofibrosis. Since reduced RBC half-life subject these mice to continuous erythroid stress, we investigated the TPO/Mpl axis in this model. In Gata1low and wild-type mice, TPO mRNA was expressed by bone marrow (BM), spleen and liver. The greatest expression (by 300-fold) was detected in liver. Gata1low livers expressed TPO mRNA levels 6-fold greater than wild-type livers. TPO protein was detected in BM, spleen, liver and peritoneum washes and plasma. The greatest levels where detected in plasma. Gata1low plasma contained TPO levels 2-fold lower than wild-type plasma, but 2-times greater than plasma from bleed wild-type mice and Mplnull mice with similar thrombocytopenia, suggesting that TPO is overproduced in Gata1low mice. JAK2 and STAT5 were easily detected in Gata1low BM bur barely detectable in wild-type BM, suggesting that in the former MPL is prompt to signaling activation. Furthermore, Gata1low LSK expressed levels of Mpl mRNA 3-times greater than wild-type cells but expressed cell-surface levels of MPL 2-times lower than wild-type cells and similar to those on LSK from TPO-treated wild-type mice, suggesting that MPL is down-modulated in Gata1low LSK. The Crispinos hypothesis that in MF activation of TPO/MPL/JAK2 induces a ribosomal deficiency hampering GATA1 mRNA translation and the realization that this axis is activated in Gata1low mice made us question the original hypothesis that reduced content of GATA1 in Gata1low MK results from deletion of lineage-specific enhancers. Microarray analyses indeed identified that Gata1low BM express a discordant ribosome signature including reduced expression of RPS24 and RPS36A, two genes mutated in Diamond Blackfan Anemia, a disease characterized by inefficient GATA1 mRNA translation. Electron microscopy identified that the cytoplasm of Gata1low MK contained poorly developed endoplasmic reticulum with rare polysomes. In conclusion, these results validate the Gata1low model as a MF model by indicating that these mice express an activated TPO/MPL axis and an abnormal ribosomal signature which may reduce efficiency of Gata1 mRNA translation.
Publication Title
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
In order to determine the imprinted transcription factor Zac1 targets, we overexpressed Zac1 in a mouse insulinoma cell line and measured the regulated expressed genes by RNA-seq. We have shown that Zac1 regulates many genes belonging to the Imprinted Gene Network, including genes coding for the extra-cellular matrix. Overall design: Determination of Zac1 target genes in transfected Min6 cells (4 biological replicates) using RNA-seq, .
Publication Title
Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In this study we investigated the changes in mRNA expression upon treatment of SH-SY5Y cells to 10M cisplatin for 72h.
Publication Title
Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples