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GSE18108
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Apoptosis is a controlled cell-death process mediated inter alia by proteins of the Bcl-2 family. Some proteins previously shown to promote the apoptotic process were found to have non-apoptotic functions as well. Microglia, the resident immune cells of the central nervous system, respond to brain derangements by becoming activated to contend with the brain damage. Activated microglia can also undergo activation-induced cell death. Previous studies have addressed the role of core apoptotic proteins in the death process, but whether or not these proteins also play a role in the activation process has not been reported. Here we explore the effect of the BH3-only protein Bid on the immunological features of microglia by subjecting both WT and Bid deficient primary neonatal microglial cultures to LPS treatment (100 ng/ml, 3h) or left untreated (control) and analyzing their transcription profiles in order to study the role of Bid.
Publication Title
Bid regulates the immunological profile of murine microglia and macrophages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
A growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis.
Publication Title
Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degrees. Sporadic and hereditary microphthalmos has been associated to heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, a transcription factor with an evolutionary conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment, in adult mice. In the trunk, Meis1 acts as a cofactor for genes of the Hox complex, mostly binding to Hox-Pbx target sequence on the DNA. By combining the analysis of Meis1 loss-of-function and conditional Meis1 functional rescue with ChIPseq and RNAseq approaches, we show that during the development of the optic cup, an Hox-free region, Meis1 binds instead to Hox/Pbx-independent Meis binding site, and coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating the expression of components of the Notch signalling pathway. Meis1 also controls the activity of genes responsible for human microphthalmia and eye patterning so that in Meis1-/- embryos, the eye size is reduced and boundaries among the different eye territories are shifted or blurred. We thus propose that Meis1 is at the core of a genetic network implicated in microphthalmia, itself representing an additional candidate for syndromic cases of these ocular malformations. Overall design: Transcriptomics and Meis1 Occupancy analysis on mouse isolated optic cups and ChIP data for histone methylation marks were obtained from about 100 eyes of E10.5 CD1 embryos.
Publication Title
Meis1 coordinates a network of genes implicated in eye development and microphthalmia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 75 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The cellular response to DNA damage is vital for maintaining genomic stability and preventing undue cell death or cancer formation. The DNA damage response (DDR), most robustly mobilized by double-strand breaks (DSBs), rapidly activates an extensive signaling network that affects numerous cellular systems, leading to cell survival or programmed cell death. A major component of the DDR is the widespread modulation of gene expression. We analyzed transcriptional responses to ionizing radiation (IR) in 5 human cell lines to elucidate the scope of this response and identify its gene targets. According to the mRNA expression profiles most of the responses were cell line-specific. Data analysis identified significant enrichment for p53 target genes and cell cycle-related pathways among groups of up-regulated and down-regulated genes, respectively.
Publication Title
Transcriptional modulation induced by ionizing radiation: p53 remains a central player.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The DNA damage response network modulates a wide array of signaling pathways, including DNA repair, cell cycle checkpoints, apoptotic pathways and numerous stress signals. The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia (A-T), is a master regulator of this network when the inducing DNA lesions are double strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combines gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation (IR) in murine lymphoid tissue. Cluster analysis revealed six major expression patterns in the data. Prominent among them was a gene cluster that contained dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of the transcription factors NF-kB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and anti-apoptotic signals were simultaneously induced, with the pro-apoptotic pathway mediated by p53, and the pro-survival pathway by NF-kB. These findings further elucidate the molecular network induced by IR and have implications for cancer management as they suggest that a combined treatment that restores the p53-mediated apoptotic arm while blocking the NF-kB-mediated pro-survival arm could be most successful in increasing the radiosensitivity of lymphoid tumors.
Publication Title
Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here we show that tumor necrosis factor (TNF) induced in human T-regulatory cells (Treg), as compared to conventional T cells (Tcon), a transcription program highly enriched for typical NF-B target genes, such as: the cytokines LTA and TNF; the TNF-receptor super family members FAS, 4-1BB and OX-40; various anti-apoptotic genes; and other important immune-response genes.
Publication Title
TNF activates a NF-kappaB-regulated cellular program in human CD45RA- regulatory T cells that modulates their suppressive function.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the application of RNA-seq analysis for high-throughput profiling of murine lungs infected with Aspergillus fumigatus. We compared the lung transcription of wildtype murine lungs and lungs from mice deficient in metabolic cytokine adiponectin. Overall design: Examination of 2 different mice strain and comparison of lung transcripts in response to Aspergillus fumigatus infection.
Publication Title
The Metabolic Cytokine Adiponectin Inhibits Inflammatory Lung Pathology in Invasive Aspergillosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mouse models of hepatocellular carcinoma (HCC) simulate specific subgroups of human HCC. We investigated hepatocarcinogenesis in Mdr2-KO mice, a model of inflammation-associated HCC, using gene expression profiling and immunohistochemical analyses. Gene expression profiling demonstrated that although Mdr2-KO mice differ from other published murine HCC models, they share several important deregulated pathways and many coordinately differentially expressed genes with human HCC datasets. Analysis of genome positions of differentially expressed genes in liver tumors revealed a prolonged region of down-regulated genes on murine chromosome 8 in three of the six analyzed tumor samples. This region is syntenic to human chromosomal regions that are frequently deleted in human HCC and harbor multiple tumor suppressor genes. Real-time RT-PCR analysis of 16 tumor samples confirmed down-regulation of several tumor suppressors in most tumors. We demonstrate that in the aged Mdr2-KO mice, cyclin D1 nuclear level is increased in dysplastic hepatocytes that do not form nodules; however, it is decreased in dysplastic nodules and in liver tumors. We found that this decrease is mostly at the protein, rather than the mRNA level. These findings raise the question on the role of cyclin D1 at early stages of hepatocarcinogenesis in the Mdr2-KO HCC model. Furthermore, we show that most liver tumors in Mdr2-KO mice were characterized by the absence of b-catenin activation. In conclusion, the Mdr2-KO mouse may serve as a model for b-catenin-negative subgroup of human HCCs characterized by low nuclear cyclin D1 levels in tumor cells and by down-regulation of multiple tumor suppressor genes.
Publication Title
Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice.
Sample Metadata Fields
Age
View Samples- Mus musculus, Homo sapiens, Saccharomyces cerevisiae
- 9 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 9 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Inactivation of the yeast IME4 gene, the yeast homologue of METTL3, was shown to result in the loss of m6A in mRNA of mutant cells grown in sporulation medium. We attempted to characterize the effects of ime4 deletion on gene expression under vegetative and meiosis-inducing conditions. The results show that in vegetatively-growing ime4-/- cells there is an increased expression of the RME1 gene (repressor of meiosis) which prevents precocious entry into the meiotic program. Mutant yeast cells showed reduced expression levels of genes involved in ribosome biogenesis and gene expression processes. Surprisingly, despite the fact that a diploid strain was analyzed, there was also a striking change in the expression level of haploid-specific genes, suggesting that RNA methylation may be used to enforce the sexual identity of diploid cells, required for the implementation of the gametogenesis program. Consistently, when cells were induced to undergo meiosis, ime4-/- diploids failed to undergo the meiotic divisions. Among the genes showing reduced expression in the mutant were IME1 and IME2, the two known inducers of meiosis. Thus, the yeast IME4 gene plays an important role in the regulation of the developmental switch from vegetative cells into gametogenesis.
Publication Title
Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.
Sample Metadata Fields
No sample metadata fields
View Samples