Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative
The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia.
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View SamplesPrecursor B-lineage acute lymphoblastic leukemia (pre-B ALL) can be subdivided into different categories based on genetic abnormalities.
Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function.
Specimen part
View SamplesThe purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD.
TCDD inhibits heart regeneration in adult zebrafish.
Treatment
View SamplesWnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore it is surprising that reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is not strongly enhanced by Wnt signaling. Here, we demonstrate that active Wnt signaling inhibits the early stage of reprogramming to iPSCs, while it is required and even stimulating during the late stage. Mechanistically, this biphasic effect of Wnt signaling is accompanied by a change in the requirement of all four of its transcriptional effectors: Tcf1, Lef1, Tcf3, and Tcf4. For example, Tcf3 and Tcf4 are stimulatory early but inhibitory late in the reprogramming process. Accordingly, ectopic expression of Tcf3 early in reprogramming combined with its loss-of-function late enables efficient reprogramming in the absence of ectopic Sox2. Together, our data indicate that the step-wise process of reprogramming to iPSCs is critically dependent on the stage-specific control and action of all four Tcfs and Wnt signaling.
Stage-specific regulation of reprogramming to induced pluripotent stem cells by Wnt signaling and T cell factor proteins.
Specimen part, Time
View SamplesWe analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Time
View SamplesVasopressin is the major hormone that regulates renal water excretion. It does so by binding to a receptor in renal collecting duct cells, triggering signaling pathways that ultimately regulate the abundance, location, and activity of the water channel protein aquaporin 2. We took an advantage of quantitative large scale proteomic technologies and oligonucleotide microarrays to quantify steady state changes in protein and transcript abundances in response to vasopressin in a collecting duct cell line, mpkCCD clone 11 (Yu et al. PNAS 2009, 106:2441-2446). This cell line originally developed by Alan Vandewalles group recapitulates vasopressin-mediated AQP2 expression and phosphorylation as seen in native colleting duct cells.
Quantitative protein and mRNA profiling shows selective post-transcriptional control of protein expression by vasopressin in kidney cells.
Specimen part, Cell line
View SamplesGenomic, proteomic, and metabolomic technologies continue to receive increasing interest from environmental toxicologists. This interest is due to the great potential of these technologies to identify detailed modes of action and to provide assistance in the evaluation of a contaminant’s risk to aquatic organisms. Our experimental model is the zebrafish (Danio rerio) exposed to reference endocrine disrupting compounds in order to investigate compound-induced changes in gene transcript profiles. Adult, female zebrafish were exposed to 0, 15, 40, and 100 ng/L of 17 alpha-ethynylestradiol (EE2) and concentration and time-dependent changes in hepatic gene expression were examined using Affymetrix GeneChip® Zebrafish Genome Microarrays. At 24, 48, and 168 hours, fish were sacrificed and liver mRNA was extracted for gene expression analysis (24 and 168 hours only). In an effort to link gene expression changes to effects on higher levels of biological organization, body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17 beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. EE2 exposure significantly affected GSI, E2, T, VTG and gene expression. We observed 1575 genes that were significantly affected (up- or down-regulated by at least 1.5-fold (p ? 0.001) in a concentration-dependent manner by EE2 exposure at either 24 or 168 hours. EE2 exposure altered transcription of genes involved in steroid hormone homeostasis, cholesterol homeostasis, retinoic acid metabolism, and cell growth and proliferation. Plasma VTG was significantly increased at 24, 48, and 168 hours (p<0.05) at 40 and 100 ng/L and at 15 ng/L at 168 hours. E2 and T were significantly reduced following EE2 exposure at 48 and 168 hours. GSI was decreased in a dose-dependent manner at 168 hours. In this study, we identified genes involved in a variety of biological functions that have the potential to be used as markers of exposure to estrogenic substances. Future work will evaluate the use of these genes in zebrafish exposed to weak estrogens to determine if these genes are indicative of exposure to estrogens with varying potencies.
Hepatic gene expression profiling using Genechips in zebrafish exposed to 17alpha-ethynylestradiol.
Sex, Specimen part, Compound, Time
View SamplesDisruption of local iron homeostasis is a common feature of neurodegenerative diseases. We focused on dopaminergic neurons, asking how iron transport proteins modulate iron homeostasis in vivo. Inactivation of the transmembrane iron exporter ferroportin had no apparent consequences. However, loss of the transferrin receptor 1, involved in iron uptake, caused profound, age-progressive neurodegeneration with features similar to Parkinsons disease. There was gradual loss of dopaminergic projections in the striatum with subsequent death of dopaminergic neurons in the substantia nigra. After depletion of 30% of the neurons the mice developed neurobehavioral parkinsonism, with evidence of mitochondrial dysfunction and impaired mitochondrial autophagy. Molecular analysis revealed strong signatures indicative of attempted axonal regeneration, a metabolic switch to glycolysis and the unfolded protein response. We speculate that cellular iron deficiency may contribute to neurodegeneration in human patients
Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons.
Age, Specimen part
View SamplesTumor associated macrophages are contributing to local invasion, angiogensis, and metastasis during the progression of many kinds of tumor including glioma
Oligodendrocyte progenitor cells promote neovascularization in glioma by disrupting the blood-brain barrier.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity.
Specimen part
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