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GSE82109
Mus musculus
23 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
mRNA from wild-type (Cre-) and MLL1-deficient (Cre+) BMDMs were analyzed via gene chip (Mouse Gene ST 2.1, Affymetrix) for relative expression changes. Isolated mRNA from Cre- and Cre+ BMDMs stimulated with classical activation signals (IFNg, LPS or IFNg+LPS) was analyzed using a gene chip panel of >40,000 RefSeq transcripts, and resulting fold expression was determined by analyzing quality-controlled expression values for validated probesets.
Publication Title
The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
The tumor suppressor TP53 is mutated in the majority of human cancers, including over 70% of pancreatic ductal adenocarcinoma (PDAC). Wild-type p53 accumulates in response to cellular stress and regulates the expression of genes that alter cell fate and constrain tumorigenesis. p53 also modulates several cellular metabolic pathways, though it remains unclear whether particular p53-regulated metabolites contribute to tumor suppression or whether metabolic alterations driven by p53 mutation sustain cancer progression. Here, we show that restoring endogenous p53 function in cancer cells derived from a murine PDAC model driven by oncogenic Kras and a regulatable p53 short hairpin RNA (shRNA) rewires glucose and glutamine metabolism leading to the accumulation of a-ketoglutarate (aKG), an obligate substrate for several chromatin modifying enzymes. p53 induces transcriptional programs characteristic of premalignant differentiation, an effect that can be partially recapitulated by addition of cell permeable aKG. Similarly, enforcing aKG accumulation in p53-deficient PDAC cells though the inhibition of oxoglutarate (aKG) dehydrogenase (Ogdh), the enzyme that consumes aKG in the tricarboxylic acid cycle, reduces tumor-initiating capacity and promotes tumor cell differentiation. Decreases in 5-hydroxymethylcytosine (5hmC), an aKG-dependent chromatin modification, are associated with the appearance of p53 mutations in the transition from premalignant to de-differentiated malignant lesions, whereas increases in 5hmC accompany tumor cell differentiation triggered by either p53 restoration or Ogdh depletion. Together these data nominate aKG as an effector of p53-mediated tumor suppression whose accumulation in p53-deficient tumors can drive tumor cell differentiation and antagonize malignant progression. Overall design: 6 samples were analyzed in duplicates of 3 conditions. 1. Control, KPsh cells grown on dox, treated with vehicle DMSO for 72 hours. 2. KPsh cells grown on dox, treated with 4mM cell permeable dimethyl-alpha ketoglutarate for 72 hours. 3. KPsh cells grown off dox for 8 days, treated with DMSO vehicle for 72 hours.
Publication Title
α-Ketoglutarate links p53 to cell fate during tumour suppression.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of this study is to survey global gene expression of total thymocytes from wild-type mice and Atg16l1 mutant (hypomorph) mice.
Publication Title
A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.
Publication Title
A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Preterm birth is an important unsolved clinical problem. Despite advanced treatments, infants who survive prematurity remain at increased risk for permanent disabilities. In approximately one-third of cases, prematurity is related to infection and/or inflammation, which renders hostile the normally receptive intrauterine environment. Proinflammatory cytokines provoke up-regulation of genes that promote uterine contractions. Using monolayer cultures of human decidual cells as a model, we profiled the global pattern of gene expression in response to cytokine challenge.
Publication Title
Inflammatory gene networks in term human decidual cells define a potential signature for cytokine-mediated parturition.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Premature birth continues to be a challenging pregnancy complication, and a body of literature indicates that inflammation can contribute to premature delivery by converting a receptive uterine environment to a hostile one. Cytokines have been demonstrated to provoke up-regulation of inflammatory genes (e.g. interleukin-1, 6, and 8, tumor necrosis factor-alpha, cyclooxygenase-2, and microsomal prostaglandin E synthase-1).
Publication Title
Inflammatory gene regulatory networks in amnion cells following cytokine stimulation: translational systems approach to modeling human parturition.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMTs) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF--dependence, we investigated the role of a Grainyhead gene (GRHL2) in oncogenic EMT. Grainyhead was specifically down-regulated in the claudin-low subclass of mammary tumors and in the basal-B subclass of breast cancer cell lines. Functionally, GRHL2 suppressed TGF--induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated, in part, by its suppression of ZEB1 expression, through direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription, and up-regulated mir200b/c as well as the TGF- receptor antagonist, BMP2. The expression of GRHL2 in the breast cancer cell line MDA-MB-231 triggered a mesenchymal-to-epithelial transition and sensitized the cells to anoikis. These results indicate that GRHL2 is a suppressor of the oncogenic EMT.
Publication Title
Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altered compensatory cytokine signaling underlies the discrepancy between <i>Flt3<sup>-/-</sup></i> and <i>Flt3l<sup>-/-</sup></i> mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The goal of this study was to determine whether there are any gene expression changes in cDC1s and cDC2s from WT, Flt3 KO, or Flt3L KO mice. Specifically whether developing in the absence of Flt3 signaling had any effects on the gene expression of the cDCs
Publication Title
Altered compensatory cytokine signaling underlies the discrepancy between <i>Flt3<sup>-/-</sup></i> and <i>Flt3l<sup>-/-</sup></i> mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To determine any expresssion changes in cDC2s from WT and CD11c-Cre Notch2f/f mice immunized with sheep red blood cells
Publication Title
Notch2-dependent DC2s mediate splenic germinal center responses.
Sample Metadata Fields
Specimen part
View Samples