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GSE2118
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
- 6 Downloadable Samples
Illumina Genome Analyzer II
Description
In this study, we employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4x108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Overall design: Examination of miRNA profile of two different ages
Publication Title
Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing.
Sample Metadata Fields
Specimen part, Race, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2500
Description
During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. Overall design: Time series. Human resting and activated T cell dUTP mRNA-Seq profiles were generated on Illumina HiSeq2500
Publication Title
Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 4000
Description
The development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Publication Title
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Gametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells. Overall design: RNA-seq and ChIP-seq analyses using wild-type and Scml2-KO spermatogenic cells
Publication Title
Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, in addition, the mechanisms underlying sublingual immunotherapy (SLIT) are still unknown.
Publication Title
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages
Publication Title
Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Temporal changes of gene expression from 1-wk- to 5-wk-old rat in kidney and lung, and the effect of prior growth inhibition on these genetic changes.
Publication Title
Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodeled the hepatic transcriptome of F2 female rats
Publication Title
Paternal high-fat diet transgenerationally impacts hepatic immunometabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether grandpaternal high-fat diet (HFD) transgenerationally remodels the transcriptome of skeletal muscle
Publication Title
Grandpaternal-induced transgenerational dietary reprogramming of the unfolded protein response in skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples