Differing from other experimental models, intranasal infection with vaccine strain of Venezuelan equine encephalitis virus, VEEV, (TC83) caused high titer infection in the brain and 90100% mortality in the C3H/HeN murine model. Intranasal infection with VEEV (TC83) caused persistent viral infection in the brains of mice without functional T-cells (-TCR -/-). While wild-type C57BL/6 mice clear infectious virus in the brain by 13 dpi, -TCR -/- maintain infectious virus in the brain to 92 dpi.
Natural killer cell mediated pathogenesis determines outcome of central nervous system infection with Venezuelan equine encephalitis virus in C3H/HeN mice.
Sex, Specimen part
View SamplesHemophagocytes are activated macrophages seen morphologically to have engulfed other hematopoietic cells. Their function is unknown. Attempts to induce these cells in vitro or purify them ex vivo have been unsuccessful.
Brief report: alternative activation of laser-captured murine hemophagocytes.
Sex, Age, Specimen part
View SamplesCNBP is a eukaryote-conserved nucleic-acid binding protein required in mammals for embryonic development. It contains seven CCHC-type zinc-finger domains and was suggested to act as a nucleic acid chaperone, as well as a transcription factor. Here, we identify all CNBP isoforms as cytoplasmic messenger RNA (mRNA)-binding proteins. Using Photoactivatable Ribonucleoside Enhanced Cross-linking and Immunoprecipitation, we mapped its binding sites on RNA at nucleotide-level resolution on a genome-wide scale and find that CNBP interacted with 3961 mRNAs in human cell lines, preferentially at a G-rich motif close to the AUG start codon on mature mRNAs. Loss- and gain-of-function analyses coupled with system-wide RNA and protein quantification revealed that CNBP did not affect RNA abundance, but rather promoted translation of its targets. This is consistent with an RNA chaperone function of CNBP helping to resolve secondary structures, thus promoting translation. Overall design: CNBP protein knockdown and RNA-seq
The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation.
No sample metadata fields
View SamplesThe concept of dedifferentiation of somatic cells into pluripotent stem cells has opened a new era in regenerative medicine. Viral transduction of defined factors has successfully achieved pluripotency derived from somatic cells. However, during the generation process of induced pluripotent stem (iPS) cells, genetic integration of certain factors may cause mutagenesis or tumorigenicity, which limits further application. Therefore, there is currently ongoing an extensive search for new methods such as transient gene delivery and oocyte-free and non-viral inducers like small molecules. Here we show that the transient delivery of embryonic stem (ES) cell-derived soluble proteins enables dedifferentiation of mouse adult somatic cells converting them into pluripotent stem cells without the introduction of certain transcription factors or genetic manipulation. During the dedifferentiation, global gene expression patterns and epigenetic status were converted from the somatic to the ES-equivalent status. Dedifferentiated somatic cells were morphologically, biologically and functionally indistinguishable from ES cells. Furthermore, the dedifferentiated cells possessed in vivo differentiation and development potential. Our results provide an alternative and safe strategy for dedifferentiation of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy.
Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Sex, Cell line, Treatment
View SamplesU3A cells stably expressing wild-type STAT1 or STAT1-CC were treated with interferon beta (10U/ml) or control for 24 hours to assess effects of stat1 modifications, interferon, and the interaction on gene expression.
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Cell line, Treatment
View SamplesThe composition of the matrix molecules is important in in vitro cell culture experiments of e.g. human cancer invasion and vessel formation. Currently, the mouse Engelbreth-Holm-Swarm (EHS) sarcoma -derived products, such as Matrigel, are the most commonly used tumor microenvironment mimicking (TMEM) matrices for experimental studies. However, since Matrigel is non-human in origin, its molecular composition does not accurately simulate human TMEM and we expect myogel to be more natural environment for human cancer cells. The environment may have crucial impact on cell behavior and gene expression.
A novel human leiomyoma tissue derived matrix for cell culture studies.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Specimen part
View SamplesMedulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Specimen part
View SamplesMedulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Specimen part
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