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GSE7342
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional p38alpha alleles, we investigated its function in postnatal development and tumorigenesis. When p38alpha is specifically deleted in the mouse embryo, fetuses develop to term but die shortly after birth, likely due to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha display increased proliferation, resulting from sustained activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Importantly, in chemical-induced liver cancer development, mice with liver-specific deletion of p38alpha show enhanced hepatocyte proliferation and tumor development that also correlates with JNK/c-Jun upregulation. Furthermore, increased proliferation of p38alpha-deficient hepatocytes and tumor cells is suppressed by inactivation of JNK or c-Jun. These results reveal a novel mechanism whereby p38alpha negatively regulates cell proliferation through antagonizing the JNK/c-Jun pathway in multiple cell types and in liver cancer development.
Publication Title
p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TMPRSS6 is a type II transmembrane serine protease and is revealed by our work to be part of a low-iron sensing pathway. When animal gets iron deficient, TMPRSS6 is required to shut off hepcidin gene, so as to allow iron to be uptaken from GI tract. The mutant mouse, which was generated by ENU mutagenesis, has developed microcytic anemia. The phenotype is caused by a splicing error in Tmprss6 gene. However, the mechanism of TMPRSS6 effect remains elusive. To gain further insight into the molecular components of the TMPRSS6 signaling pathway, we overexpressed either TMPRSS6 or its mutant version of protein in human liver carcinoma cell line HepG2 cells, and compared the transcription status betweem these two treatments.
Publication Title
The serine protease TMPRSS6 is required to sense iron deficiency.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment.
Publication Title
Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution.
Sample Metadata Fields
Sex, Age, Disease
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microglia colonize the brain parenchyma at early stages of development and accumulate in specific regions where they actively participate in cell death, angiogenesis, neurogenesis and synapse elimination. A recurring feature of embryonic microglial distribution is their association with developing axon tracts which, together with in vitro data, supports the idea of a physiological role for microglia in neurite development. Yet the demonstration of this role of microglia is still lacking. Here, we have studied the consequences of microglial dysfunction on the formation of the corpus callosum, the largest connective structure in the mammalian brain, which shows consistent microglial accumulation during development. We studied two models of microglial dysfunction: the loss-of-function of DAP12, a key microglial-specific signaling molecule, and a model of maternal inflammation by peritoneal injection of LPS at E15.5. We performed transcriptional profiling of maternally inflamed and Dap12-mutant microglia at E17.5. We found that both treatments principally down-regulated genes involved in nervous system development and function, particularly in neurite formation. We then analyzed the functional consequences of these microglial dysfunctions on the formation of the corpus callosum. We also took advantage of the Pu.1-/- mouse line, which is devoid of microglia. We now show that all three models of altered microglial activity resulted in the same defasciculation phenotype. Our study demonstrates that microglia are actively involved in the fasciculation of corpus callosum axons.
Publication Title
Microglia shape corpus callosum axon tract fasciculation: functional impact of prenatal inflammation.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show, using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and 0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios.
Publication Title
Comparison of gene expression profiles of conjunctival cell lines with primary cultured conjunctival epithelial cells and human conjunctival tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 58 Downloadable Samples
NextSeq 500
Description
Lgr5+ adult intestinal stem cells are highly proliferative throughout life. Single Lgr5+ stem cells can be cultured into 3D epithelial organoids containing all cell types at nearnormal ratios. Culture conditions to generate the main cell types have been established previously, but signals inducing the various types of enteroendocrine cells (EECs) have remained elusive. Here we generate quiescent Lgr5+ stem cells in vitro by inhibition of the EGF-receptor (EGFR) and mitogen-associated protein kinase (MAPK) signaling pathways in organoids, a state that can be readily reversed. Quiescent Lgr5+ stem cells gain a distinct molecular signature, biased towards EEC differentiation. Indeed, combined inhibition of Wnt, Notch and MAPK pathways efficiently generates a diversity of EEC subtypes in vitro. Our observations uncouple Wnt-dependent stem cell maintenance from EGF-dependent proliferation and cell fate choice, and provide an in vitro approach for the study of the elusive EECs. Overall design: We established a stable culture of quiescent Lgr5+ intestinal stem cells in culture. These highly resemble quiescent secretory precursors, which has high EEC differentiation potential. Following on this lead, we elucidated what signals are required to generate EEC cells of all varieties, and provide a method to produce these EEC cells in large numbers.
Publication Title
Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Abstract Two major dendritic cell (DC) subsets have been described in the islets of mice: The immunogenic CD8-CD11b+ DCs and the tolerogenic CD8+CD103+ DCs. We have recently reported on reduced numbers of the minor population of tolerogenic CD8+CD103+ DCs in the pancreas of 5 week old pre-diabetic non-obese diabetic (NOD) mice. Aim: To analyze also the larger subset of CD11c+CD8- DCs isolated from the pancreas of pre-diabetic NOD mice 1) for maturation and tolerance inducing molecules found abnormally expressed on CD8+CD103+ DCs, and 2) for genome-wide gene expression to further elucidate abnormalities in underlying gene expression networks. Methods: CD11c+CD8- DCs were isolated from 5 week old C57BL/6 and NOD pancreas. Expression of cell surface markers including CD86, CCR5, CD11b, CD103, Clec9a, CD24 and CD200R3 were measured by FACS. Genome-wide gene expression by microarray was assessed during the steady state and after in vitro LPS stimulation. Results: The steady state pancreatic CD11c+ CD8- DCs during the pre-diabetic stage showed: 1) A reduced expression of several gene networks important for the prime functions of the cell, such as for cell renewal, immune stimulation and immune tolerance induction, for migration and for the provision of growth factors for beta cell regeneration. This general deficiency state was corroborated by a reduced in vivo proliferation (BrdU incorporation) of the cells and the reduced expression in FACS analysis of CD86, CCR5, CD103, Clec9a, CD24 and CD200R3 on the cells. 2) A hyper reactivity of these cells to LPS correlated with an enhanced pro-inflammatory state characterized by altered expression of a number of classical pro-inflammatory factors and cytokines. Conclusion: The NOD CD11c+CD8- DCs seem to be Janus-faced depending on the conditions: Deficient in steady state with reduced immune stimulation capabilities also for tolerance induction; over-inflammatory with a molecular profile suggesting a preferential stimulatory capacity for Th1 cells when encountering a Pathogen-Associated Molecular Pattern (PAMP) in the form of LPS.
Publication Title
The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo.
Publication Title
Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Identifying the effect of the co-regulator Hic-5 (TGFB1I1) and TGFB on the transcriptional profile of WPMY human prostate fibroblast cells with view to further elucidating the broader biological role of Hic-5 and TGFB on fibroblast.
Publication Title
VDR activity is differentially affected by Hic-5 in prostate cancer and stromal cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
KATP opposes depolarization of cells in the heart, smooth muscle, and other tissues by permitting the efflux of potassium ions and this efflux is evidently required to prevent unopposed vasoconstriction and insufficiency of coronary artery blood flow triggered by one or more cytokines induced in response to LPS. The cytokine(s) involved must elicit a dysfunctional response in the Kir6.1-deficient environment, and to gain further insight into the effects of the mutation, we examined the transcriptional status of whole heart, isolated from normal C57BL/6J mice or KcnJ8Md/Md mice, before and after injection of 1 g of LPS
Publication Title
ATP-sensitive potassium channels mediate survival during infection in mammals and insects.
Sample Metadata Fields
No sample metadata fields
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