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GSE23935
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma.
Publication Title
TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
Analysis of musashi2 contribution towards maintaing myelodysplastic phenotype in stem cells. We find that musashi2 plays an integral role in maintaining the myelodysplastic phenotype Overall design: Control, NUP98-HOXD13; NHD13, NHD13/MSI2 bone marrow was transplated allowed to engraft into lethally irradiated congenic CD45.1 animals. Mice were then fed doxycycline to induce MSI2 overexpression. Mice were induced for 3 months and then CD45.2 Lineage lo Sca1+ and Kit+ cells were sorted and then assessed for gene expression.
Publication Title
MSI2 is required for maintaining activated myelodysplastic syndrome stem cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam celllike cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
Publication Title
Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Maternal IL10 deficiency elevates susceptibility to fetal loss induced by the model Toll-like receptor agonist lipopolysaccharide, but the mechanisms are not well elucidated. Here we show that Il10 null mutant (Il10-/-) mice exhibit altered local T cell responses in pregnancy, exhibiting pronounced hyperplasia in para-aortic lymph nodes draining the uterus with >6-fold increased CD4+ and CD8+ T cells compared with wild-type controls. Amongst these CD4+ cells, Foxp3+ Treg cells were substantially enriched, with 11-fold higher numbers at day 9.5 post coitum (pc). Lymph node hypertrophy in Il10-/- mice was associated with more activated phenotypes in dendritic cells and macrophages, with elevated expression of MHCII, scavenger receptor and CD80. Affymetrix microarray revealed an altered transcriptional profile in Treg cells from pregnant Il10-/- mice, with elevated expression of Ctse (cathepsin E), Il1r1, Il12rb2 and Ifng. In vitro, Il10-/- Treg cells showed reduced steady state Foxp3 expression, and polyclonal stimulation caused greater loss of Foxp3 and reduced capacity to suppress IL17 in CD4+Foxp3- T cells. We conclude that despite a substantially expanded Treg cell pool, diminished stability of Treg cells, increased numbers of effector T cells, and altered phenotypes in dendritic cells and macrophages in pregnancy all potentially confer vulnerability to inflammation-induced fetal loss in Il10-/- mice. These findings suggest a pivotal role for IL10 in facilitating robust immune protection of the fetus from inflammatory challenge and suggest IL10 deficiency could contribute to human gestational disorders where altered T cell responses are implicated.
Publication Title
Unstable Foxp3+ regulatory T cells and altered dendritic cells are associated with lipopolysaccharide-induced fetal loss in pregnant interleukin 10-deficient mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis. To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53. Using statins and sterol biosynthesis intermediates, we demonstrate that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with the sterol gene promoters at least partly via the SREBP transcription factors. Finally, p53 mutation correlates with higher levels of sterol biosynthesis genes in human breast tumors. This activity of mutant p53 not only contributes insight into breast carcinogenesis, but also implicates the mevalonate pathway as a new therapeutic target for tumors bearing such mutations in p53.
Publication Title
Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNa2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNa2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNß also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response. Overall design: HuH7 cells were treated with 10000 units/ml of IFN a2 and RNA was isolated 3 days post-treatment
Publication Title
Type I Interferon Regulates the Expression of Long Non-Coding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Iron is an essential cofactor for enzymes involved in numerous cellular processes. We analyzed the metabolomes and transcriptomes of yeast grown in iron-rich and iron-poor media to determine which biosynthetic processes are altered when iron availability falls.
Publication Title
Metabolic response to iron deficiency in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2500
Description
B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cell division and is linked to DNA hypomethylation and gene regulation. Conversely, accumulation of DNA methylation in B cell differentiation is less apparent. To determine the role of de novo DNA methylation in B cell differentiation, the de novo DNA methyltransferases, Dnmt3a and Dnmt3b, were deleted in B cells resulting in phenotypically normal B cell development in the bone marrow, spleen and lymph nodes. However, upon immunologic challenge, mice deficient for Dnmt3a and Dnmt3b (Dnmt3-deficient) accumulated more antigen-specific B cells and bone marrow chimeras showed this was cell-autonomous. Additionally, a five-fold increase in splenic and bone marrow plasma cells was observed. Molecular analysis revealed that Dnmt3-deficient bone marrow plasma cells failed to repress gene expression to the same level as their Dnmt3ab-sufficient counterparts. This was coupled with a failure of Dnmt3-deficient germinal center B cells and plasma cells to gain and/or maintain DNA methylation at several thousand loci that were clustered in enhancers of genes that function in B cell activation and homing. Analysis of chromatin accessibility showed Dnmt3-deficient plasma cells had increased accessibility at several genes involved in hematopoiesis and B cell differentiation. These data show that de novo DNA methylation limits B cell activation, proliferation and differentiation, and support a model whereby DNA methylation represses the aberrant transcription of genes silenced in B cell differentiation to maintain plasma cell homeostasis. Overall design: Naïve lymph node B cells (B220+ GL7- Fas-), Phycoerythrin-specific germinal center B cells (B220+ GL7+ Fas+ PE+), and bone marrow plasma cells (CD138+) were compared between Cd19cre/wtDnmt3afl/flDnmt3bfl/fl (Dnmt3-deficient) and littermate control Cd19wt/wtDnmt3afl/flDnmt3bfl/fl (Dnmt3-sufficient) mice using RRBS, RNA-seq, and ATAC-seq. Naïve lymph node B cells were taken from naïve mice, whereas PE-specific germinal center B cells and bone marrow plasma cells were isolated from mice that had been immunized with phycoerythrin 30 days prior. This Series includes the RNA-seq component of the study.
Publication Title
B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the role of EZH2 in Plasmablast function EZH2 was inducibly deleted using tamoxifen and B cells stimulated to differentiate with LPS in vivo. After 3 days, CD138+ cells were enriched from the spleens and RNA-seq was performed to identify the genes targeted by EZH2 for repression. Overall design: RNAseq on control or EZH2-deficient murine plasmablasts.
Publication Title
EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples