Vanin1, a regulator of vitamin B5 metabolism, is expressed by sarcoma tumors. We evaluated its impact on sarcoma growth by using sarcoma cell lines derived from p16p19Vnn1-deficient mice and further transduced with an oncogenic RasV12 oncogene (R tumors) in the presence or not of a catalytically active (VR tumors) or mutated (VdR tumors) Vnn1 isoform.
Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Specimen part
View SamplesAn investigation of the global gene expression signatures of murine hematopoietic stem cell differentiation during steady state hematopoiesis.
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Specimen part
View SamplesAccumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis- multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/ Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.
eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.
Specimen part, Cell line, Treatment
View SamplesWe used Arabidopsis full-genome microarrays to characterize plant transcript accumulations at different stages of infection with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis : initiation (< 1 dpi) and maintenance of infection (> 4 dpi).
An Arabidopsis (malectin-like) leucine-rich repeat receptor-like kinase contributes to downy mildew disease.
Specimen part
View SamplesPlasmacytoid dendritic cells (pDC) are the major source of type I and type III interferons (IFN-I/III) during viral infections, in response to triggering of endosomal Toll Like Receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Interestingly, this function is restricted to a minor fraction of pDC (Zucchini et al. Int. Immunol. 2008). In this project, we aimed at identifying the molecular pathways involved in inducing IFN-I/III production in this minor faction of pDC during in vivo infection by the mouse cytomegalovirus (MCMV). To achive this goal, we infected with MCMV Ifnb1Eyfp mice, in which IFN-producing pDC can be detected by YFP expression (Scheu et al. PNAS 2008). Thanks to this model, we were able to sort three distinct subsets of pDC: CD86-YFP- (not activated, non IFN-producing), CD86+YFP- (activated, non IFN-producing) and CD86+YFP+ (activated, IFN-producing) and to perform microarray analysis. This allowed us to select genes differentially expressed among these three subsets and to mine these data in order to identify the related signaling pathways.
The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection.
Specimen part, Treatment
View SamplesTo study the role of the plant hormone jasmonate in regulating stress-induced allocation of photosynthetic products between growth- and defense-related processes, we used RNA-sequencing to query the Arabidopsis transcriptome at high temporal resolution over 24 h after treatment with the bacterial toxin coronatine (COR), a high-affinity agonist of the JA receptor, or with a mock solution to account for diurnal changes in gene expression. These data establish a fine-scale view of the kinetics of jasmonate signaling, as well as of the diurnal patterns of gene expression.
Temporal Dynamics of Growth and Photosynthesis Suppression in Response to Jasmonate Signaling.
Age, Specimen part, Treatment, Time
View SamplesWhole blood RNA-seq was leveraged to explore gene expression changes induced in mice 24 hours after immunisation with a second dose of a licensed vaccine against capsular group B meningococcus, one of the vaccines components, or one of several comparator groups. Overall design: mRNA was profiled from RNA extracted from mouse whole blood, 5-6 samples per group, using an Illumina HiSeq4000
Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B meningococcal vaccine, 4CMenB, to the membrane-bound endotoxin of its outer membrane vesicle component.
Sex, Cell line, Subject
View SamplesThe Endoplasmic Reticulum–Mitochondria Encounter Structure (ERMES) is a protein complex that tethers the two organelles and creates the physical basis for communication between them. ERMES functions in lipid and calcium exchange between the ER and mitochondria, mitochondrial protein import and maintenance of mitochondrial morphology and genome. Here we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of ERMES known roles in calcium regulation, phospholipid biosynthesis or mitochondrial biology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our study reveals that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels. Overall design: various mutants
Endoplasmic reticulum-mitochondria junction is required for iron homeostasis.
Subject
View SamplesTransgenic PiZ mice have been genetically engineered to express ATZ and have been a valuable experimental model for studing liver disease associated with AAT deficiency. ATZ accumulates in these mice within the ER of hepatocytes in a nearly identical manner to livers of affected patients. To investigate the pathogenesis of liver damage induced by ATZ, we performed gene expression analysis in livers of 6-week-old PiZ mice and strain-, age-, and gender-matched wild-type mouse controls. All samples were processed on Affymetrix Mouse 430A 2.0 arrays using GeneChip 3-IVT Plus and Hybridization Wash and Stain kits by means of Affymetrixs standard protocols. The analysis indicated that most genes upregulated in PiZ livers were associated with response to unfolded proteins, ER nuclear signaling pathway, and response to protein stimulus.
Activation of the c-Jun N-terminal kinase pathway aggravates proteotoxicity of hepatic mutant Z alpha1-antitrypsin.
Specimen part
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