Gene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3
1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation.
No sample metadata fields
View SamplesHuman umbilical vein endothelial cells (HUVECs) were incubated for 48 h after transfection of scrambled siRNA or siRNA targeting Jmjd6 .
Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1.
Specimen part, Treatment
View SamplesDiffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.
Treatment
View SamplesWe analyzed the genome-wide expression by RNA-seq of a yeast strain that expresses Cas9d and a guideRNA targeted to the GAL10 locus (called +116), which inhibits GAL10 ncRNA expression from the antisense strand. We compared this strain to a strain expressing a scrambled guideRNA. The goal was to examine the effects of ncRNA inhibition and to examine if CRISPR inhibition of gene expression has off-target effects. We find that CRISPR-mediated inhibtion of GAL10 ncRNA only significantly changes expression of transcripts at the GAL1-10 locus, showing that CRISPR is highly specific, and that GAL10 ncRNA only control genes at the GAL locus. Overall design: RNA-seq of 2 strains with CRISPR scrambled and 2 strains with CRISPR +116, the latter of which inhibits GAL10 ncRNA
Single-Molecule Imaging Reveals a Switch between Spurious and Functional ncRNA Transcription.
Cell line, Subject
View SamplesBACKGROUND: Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment.
Dynamics of dendritic cell maturation are identified through a novel filtering strategy applied to biological time-course microarray replicates.
Specimen part
View SamplesTranscriptome analysis of adult hematopoietic stem cells (HSC) and their progeny has informed our understanding of blood differentiation and leukemogenesis, but a similarly transformative analysis of the embryonic origins of hematopoiesis is lacking. To address this issue, we acquired gene expression profiles of developing HSC purified from over 2500 dissected murine embryos and adult mice, and applied a network biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs emerging from hemogenic endothelium, and definitive HSCs. We functionally validated several candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knock-down in zebrafish embryos, confirming changes in the expression of HSC markers runx1 and c-myb in the aorta-gonads-mesonephros (AGM), the site of definitive HSC specification. Moreover, we found that HSCs derived from differentiating embryonic stem cells in vitro (ESC-HSC) most closely resemble definitive HSC, yet lack a signature indicative of specification by Notch signaling, which likely accounts for their deficient lymphoid development. Our analysis and accompanying web resource will accelerate the characterization of regulators of HSC ontogeny, facilitate efforts to direct hematopoietic differentiation and cell fate conversion, and serve as a model to study the origins of other adult stem cells.
The transcriptional landscape of hematopoietic stem cell ontogeny.
Specimen part
View SamplesWe established and characterized a new recessive mutant mouse line kta41 with a point mutation in Scube3 at position 882. The mutant line was detected by screening for morphological abnormalities in the Munich ENU-mutagenesis program. The mutation was mapped by microsatellite markers to mouse chromosome 17, between markers D17MIT29 and D17MIT101. Candidate gene approaches failed due to the low recombination frequency and the high number of genes within the mapped interval. Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys). We did a broad phenotypic analysis of the mutant mouse line in the German Mouse Clinic (GMC), and followed up the found alterations by detailed phenotypic characterization. Scube3-kta41-/- mice show a series of phenotypic alterations, mainly in the skeleton, behavior and neurological abnormalities as well as changes in physiology, metabolism and immune status.
The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.
Sex, Age
View SamplesTreatment induced senescence (TIS) is a terminal cell cycle arrest program, increasingly recognized as a tumor suppressor mechanism complementing apoptosis in response to standard chemotherapy regimens. In particular cells with blocked apoptotic pathways rely on senescence as the only remaining failsafe mechanism to keep the neoplastic growth in check. However, little is known about biological properties, long-term fate of senescent tumor cells and their impact on the microenvironment.
Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
No sample metadata fields
View SamplesCohesin acetylation by Eco1 during DNA replication establishes sister chromatid cohesion. We show that acetylation makes cohesin resistant to Wapl activity from S-phase until mitosis. Wapl turns out to be a key regulator of cohesin dynamics on chromosomes by controling cohesin maintenance following its establishment in S-phase and its role in chromosome condensation.
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
No sample metadata fields
View Samples