In neural stem cells, stimulation of the death receptor CD95 does not trigger apoptosis but resulted in increased stem cell survival and neuronal specification via activation of the Src /PI3K /AKT/mTOR signalling pathway. To further characterize CD95-dependent neural stem cell survival and differentiation we used conventional gene expression profiling combined with translation state array analysis. Mouse neural stem cells grown in neurosphere cultures were stimulated with a trimerized CD95L construct (CD95L-T4) and total as well as polysomal bound RNA was isolated 48 hours after stimulation and analysed by microarrays. CD95L-T4 treatment induced a global increase in ribosome-bound mRNA and protein translation as well as changes on genes involved in neurogenesis, protein synthesis and transcription factors.
The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair.
Sex, Treatment
View SamplesMice have been treated with NOX-A12. Whole BM cells have been harvested, RNA isolated, and gene expression profiling was performed on cDNA using Mouse Genome 430 2.0 array. Untreated mice have been used as control.
SDF-1 inhibition targets the bone marrow niche for cancer therapy.
Treatment
View SamplesWe established a neuron-specific Argonaute2:GFP-RNA immunoprecipitation followed by high throughput sequencing (AGO2-RIP-seq) to analyse the regulatory role of miRNAs in mouse hippocampal neurons. Using this technique, we identified more than two thousand miRNA target genes in hippocampal neurons, regulating essential neuronal features such as axon guidance and transcription. Furthermore, we found that stable inhibition of the highly expressed miR-124 in hippocampal neurons led to significant changes in the AGO2 binding of target mRNAs, resulting in subsequent upregulation of numerous miRNA target genes. Our data suggest that target redundancies are common among microRNA families. Together, these findings greatly enhance our understanding of the mechanisms and dynamics through which miRNAs regulate their target genes in neurons. Overall design: Analysis of the miRNA targetome in hippocampal neurons after inhibition of 2 different miRNAs. AAV5 injections into the hippocampus of adult C57BL/6 mice producing either of the following under a synapsin promoter: GFP only (Samples beginning with ''GFP124…'' or ''GFP125…''), GFP-miR124sp (Samples beginning with ''miR124…''), GFP-miR125sp (Samples beginning with ''miR125…''), GFP-AGO2-miR292sponge (samples ending with ''…292''), GFP-AGO2-miR124sponge (samples ending with ''…124''), GFP-AGO2-miR125sponge (samples ending with ''…125''). All other samples were sham-injected.
Identification of the miRNA targetome in hippocampal neurons using RIP-seq.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line, Treatment
View SamplesThe goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia).
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line
View Samplesp53 induces cell death upon DNA damage, but this may not confer all of its tumor suppressor activity. We report that p53 activation enhances the processivity of DNA replication, as monitored by multi-label fiber assays, whereas removal of p53 reduces fork progression. This was observed in tumor-derived U2OS cells, but also in murine embryonic fibroblasts with heterozygous or homozygous p53 deletion, and in freshly isolated thymocytes from mice with differential p53 status. Mdm2, a p53-inducible gene product, similarly supported DNA replication even in p53-deficient cells, suggesting that sustained Mdm2-expression is at least one of the mechanisms allowing p53 to prevent replicative stress. Thus, p53 helps to protect the genome during S phase, by preventing the occurrence of stalled or collapsed replication forks. These results expand p53’s tumor-suppressive functions, adding to the ex-post model (elimination of damaged cells) an ex-ante activity, i.e. the prevention of DNA damage during replication. Overall design: Expression profiling by high throughput sequencing
p53 Activity Results in DNA Replication Fork Processivity.
Specimen part, Cell line, Subject
View SamplesIn this project, we studied a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the GATA1 transcription factor (called GATA1s mutation). The model was generated through retroviral insertional mutagenesis in Gata1s mutant fetal liver progenitors. In this study, we analyzed the dependency of these leukemic cells on the Gata1s mutant protein.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Cell line, Treatment
View SamplesThe goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Cell line
View SamplesThe goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part
View SamplesThe goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part
View Samples