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GSE18907
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.
Publication Title
Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There are an estimated 21million diabetics in the United States and 150 million diabetics worldwide. The World Health Organization anticipates that these numbers will double in the next 20 years. Metabolic syndrome is a well recognized set of symptoms that increases a patients risk of developing diabetes. Insulin resistance is a factor in both metabolic syndrome and Type 2 diabetes. It is characterized by decreased insulin stimulated glucose uptake in peripheral tissues, decreased adiponectin levels, increased adipocyte FFA and cytokine production, and increased insulin and hepatic glucose output. Prevention or reversal of insulin resistance should serve as an important strategy in addressing the growing health concerns posed by the Diabetes epidemic. While increased adiposity is associated with insulin resistance, the role of the cell types present within adipose (adipocytes, pre-adipocytes, endothelial cells, macrophages, fibroblasts, leukocytes and smooth muscle cells) in insulin resistance is unclear. In an effort to begin dissection of this question, we examined the transcriptional response of the buoyant and non-buoyant fractions isolated from insulin sensitive or TNF induced insulin resistant hMSC derived adipocytes before and after treatment with insulin.
Publication Title
Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 317 Downloadable Samples
Illumina HiSeq 2500
Description
We perfomed single-cell RNA-sequnecing of around 10,000 cells from normal human liver tissue to construct a human liver cell atlas. We reveal previously unknown subtypes in different cell type compartments. We also use our normal liver cell atlas to infer perturbed phenoytpes of cells from HCC samples, human cells engrafted into a mouse liver and liver organoids. Overall design: Single cells were isolated from human liver resection specimens and then sorted by FACS into 384 well plates in a unbiased way and on the basis of cell surface markers for distinct cell types. ScRNA-seq was done using the mCelSeq2 protocol cellbarcodes_cellid.csv Supplemetary file contains cellds and one of the 192 unique cellbarcode associated with the cellid.
Publication Title
A human liver cell atlas reveals heterogeneity and epithelial progenitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Interferon-γ-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response (SVR) to treatment with pegylated interferon (pegINF)- and ribavirin. Non-response to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with SVR rates >90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN- therapy. We analyzed IFN signaling and ISG expression in liver samples from patients with acute hepatitis C (AHC), patients with chronic hepatitis (CHC), and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN- or IFN-, as reference sets. Expression levels of 100s of genes, primarily those regulated by IFN-, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN- signaling, we did not observe differences in expression of SOCS1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN- signaling), was upregulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. In conclusion, differences in expression of ISGs might account for the greater response of patients with AHC, compared to those with CHC, to treatment with pegINF- and ribavirin. Specifically, USP18 is upregulated in liver samples of patients with CHC that do not respond to therapy, but not in patients with AHC.
Publication Title
Interferon-γ-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response (SVR) to treatment with pegylated interferon (pegINF)- and ribavirin. Non-response to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with SVR rates >90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN- therapy. We analyzed IFN signaling and ISG expression in liver samples from patients with acute hepatitis C (AHC), patients with chronic hepatitis (CHC), and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN- or IFN-, as reference sets. Expression levels of 100s of genes, primarily those regulated by IFN-, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN- signaling, we did not observe differences in expression of SOCS1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN- signaling), was upregulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. In conclusion, differences in expression of ISGs might account for the greater response of patients with AHC, compared to those with CHC, to treatment with pegINF- and ribavirin. Specifically, USP18 is upregulated in liver samples of patients with CHC that do not respond to therapy, but not in patients with AHC.
Publication Title
Interferon-γ-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Drosophila melanogaster
- 15 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Centrosome defects are a common feature of many cancers. Surprisingly, flies can proceed through the majority of development without centrosomes or with amplified centrosomes in most of their cells. It is unclear whether this is because centrosome defects do not cause many problems in Drosophila cells, or because they can adapt to cope with any problems that arise. Indeed, centrosome loss and centrosome amplification predispose fly brain cells to form tumours. Here we assess how centrosome loss or centrosome amplification perturbs cell physiology by profiling the global transcriptome of Drosophila larval brains and imaginal discs that either lack centrosomes or have too many centrosomes.
Publication Title
Centrosome loss or amplification does not dramatically perturb global gene expression in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep), or its specific down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.
Publication Title
EZH2 is essential for glioblastoma cancer stem cell maintenance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the mechanisms that underlie ESFT CSC development. We show that the EWS-FLI-1 fusion gene, associated with 85%-90% of ESFTs and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2, and NANOG in human pediatric MSCs (hpMSCs) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSCs expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWS-FLI-1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene, SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype.
Publication Title
EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.
Sample Metadata Fields
Specimen part
View Samples