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GSE34529
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The relationships between cancer cells and the microenvironment play a critical role in cancer growth and development. The bone stroma consists of mesenchymal stem cells (MSCs) and mature osteoblasts that promote cancer growth. Yet it is not completely understood what are the molecular processes guiding cancer cells progression to the bone. In this study, a co-culture assay and subsequent gene profiling arrays were used to compare the gene expression profile of a pre-osteoblastic cell line (MBA-15) with that of a mammary adenocarcinoma (DA3) cells. Following co-culture, cells were separated by magnetic beads based on the expression of CD326 antigen. RNA was purified and hybridized on gene expression array. The gene expression pattern changes were followed by qRT-PCR. We demonstrate that co-cultured DA3 cells express elevated levels of genes that regulate growth and responses to both hormonal stimulus and wounding, as well as reduced expression of genes related to lipid metabolism. Also, co-cultured pre-osteoblastic cells showed reduced expression of cell-junction genes. The study presents a simplified model system, composed of pre-osteoblastic and mammary cancer cells, that potentially mimics the molecular interactions in the tumor microenvironment which contribute to tumor-progression.
Publication Title
Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Schizosaccharomyces pombe
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We show that the sensitivity of tsc mutant cells to rapamycin is mediated by TORC1 and can be suppressed by overexpression of the 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling. suppressed by overexpression of the putative 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel master regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling.
Publication Title
Isp7 is a novel regulator of amino acid uptake in the TOR signaling pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The coupling between cell-cycle exit and onset of differentiation is a common feature throughout the developing nervous system, but the mechanisms that link these processes are mostly unknown. Although the transcription factor Pax6 was implicated in both proliferation and differentiation of multiple regions within the CNS, its contribution to the transition between these successive states remains elusive. To gain insight into the role of Pax6 during the transition from proliferating progenitors to differentiating precursors, we investigated cell-cycle and transcriptomic changes occurring in Pax6- retinal progenitor cells (RPCs). Our analyses revealed a unique cell-cycle phenotype of the Pax6-deficient RPCs, which included a reduced number of cells in the S phase, an increased number of cells exiting the cell cycle, and delayed differentiation kinetics of Pax6- precursors. These alterations were accompanied by co-expression of factors that promote (Ccnd1, Ccnd2, Ccnd3) and inhibit (P27kip1 and P27kip2) the cell cycle. Further characterization of the changes in transcription profile of the Pax6-deficient RPCs revealed abrogated expression of multiple factors which are known to be involved in regulating proliferation of RPCs, including the transcription factors Vsx2, Nr2e1, Plagl1 and Hedgehog signaling. These findings provide novel insight into the molecular mechanism mediating the pleiotropic activity of Pax6 in RPCs. The results further suggest that rather than conveying a linear effect on RPCs, such as promoting their proliferation and inhibiting their differentiation, Pax6 regulates multiple transcriptional networks which function simultaneously, thereby conferring the capacity to proliferate, assume multiple cell fates and execute the differentiation program into retinal lineages.
Publication Title
Pax6 is required for normal cell-cycle exit and the differentiation kinetics of retinal progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, while evidence supports the replicative capacity of adult beta cells in vivo, attempts at expanding human islet cells in tissue culture resulted in loss of beta-cell phenotype. Using a genetic lineage-tracing approach we have provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT). Epigenetic analyses indicate that key beta-cell genes maintain a partially open chromatin structure in expanded BCD cells, although they are not transcribed. Here we report that BCD cells can be induced to redifferentiate by a combination of soluble factors. The redifferentiated cells express beta-cell genes, store insulin in typical secretory vesicles, and release it in response to glucose. The redifferentiation process involves mesenchymal-epithelial transition, as judged from changes in gene expression. Moreover, inhibition of the EMT effector SLUG using shRNA results in stimulation of redifferentiation. BCD cells also give rise at a low rate to cells expressing other islet hormones, suggesting transition through an islet progenitor-like stage during redifferentiation. These findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug screening.
Publication Title
Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Inbred congenic strain B6.C6.132.54/Vad was created using C57BL/6ByJ background and BALB/cJ donor strains. Flanking background markers at chr. 6: 75.9 Mb (rs4226008, NCBI Mouse Build 36 / dbSNP Build 126) and 122.3 Mb (rs3023093), and limiting donor markers at 81.9 Mb (rs4226024) and at 91.8 Mb (rs3712161) defined the introgressed region. We concluded the segment size must be between 9.9 Mb and 46.4 Mb. In a Quantitative Trait Gene identification study we compared brain (without cerebellum) gene expression between progenitors and congenics. Such comparisons can facilitate identification of cis-regulated genes and to establish genetic control of a complex phenotype whose expression is associated with the introgressed chromosome segment.
Publication Title
Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 85 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human CD14 positive monocytes were purified from healthy volunteers blood and cultured in vitro for 4, 12, 24, 72 hours. While culturing, macrophages were activated alternatively with interleukin-4 (IL-4 100 ng/ml) or classically with interferon-gamma (IFNg 100 ng/ml)+tumor necrosis factor (TNF 50 ng/ml) or left without activation. Simultaneously, macrophages were also treated with vehicle (DMSO:ethanol) or 1mM synthetic PPARg agonist, Rosiglitazone. We used Affymetrix microarrays (U133Plus 2.0) to analyze activation and PPARg-induced gene expression changes.
Publication Title
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
C57Bl/6 wild-type and STAT6 KO mice were used to study PPARg and IL-4 signaling. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and frech media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.
Publication Title
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Conditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.
Publication Title
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Vitamin D is a secosteroid that has multiple regulatory roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer's disease, Parkinson's disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 induced expression of SKN-1 target genes, but not canonical targets of IRE-1/XBP-1. Vitamin D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented the toxicity caused by human ß-amyloid. Our observation that vitamin D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with a vitamin D deficiency. Overall design: The experimental design consisted of contrasting gene expression data derived from RNA extracted from pools of synchronized aged worms. L4 worms were placed on either vehicle (DMSO) or Vitamin D (100uM) for 44 hours prior to extraction. A pool of 50 worms was considered a single biological replicate. For the Vitamin D treated group, there were 6 independent biological replicates, and were compared with a group of untreated (vehicle) wild-type N2 animals, also using 6 biological replicates.
Publication Title
Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1.
Sample Metadata Fields
Treatment, Subject
View Samples