Tamoxifen, a selective estrogen receptor modulator, is widely used in research and clinically in patients. Tamoxifen injection (3 consecutive days, intraperitoneal, 5mg/20g mouse body weight) causes dramatic rearrangement of the gastric mucosa with loss of > 90% of PCs, a 6-fold increase in proliferation in stem/progenitor cells, and morphological changes in the ZCs in the bases of gastric-units.
Identification of alanyl aminopeptidase (CD13) as a surface marker for isolation of mature gastric zymogenic chief cells.
Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Age, Specimen part, Treatment
View SamplesMethionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Age, Specimen part
View SamplesIdentify differentially expressed genes related to the neurodegenerative process in a new animal model of hepatic encephalopathy (HE).
Cerebellar neurodegeneration in a new rat model of episodic hepatic encephalopathy.
Specimen part, Treatment
View SamplesDeafness due to the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, non-mammalian animals (e.g. birds, amphibian and fish) regenerate damaged hair cells. In order to better understand the reasons underpinning such regeneration disparities in vertebrates, we set out to define the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line at high resolution. We performed RNA-Seq analyses on regenerating support cells purified by fluorescence activated cell sorting (FACS). The zebrafish lateral line provides an experimentally accessible system to define the complex signaling events triggered by injury and regeneration, because these cells can be acutely killed by exposure to neomycin, after which they regenerate rapidly. Lateral line hair cells are located in the center of a mechanosensory organ known as the neuromast and are surrounded by inner support cells and an outer ring of mantle cells. Tg(sqET20) larvae express GFP strongly in mantle cells and to a lesser degree in inner support cells. We isolated GFP positive and GFP negative cells from 5 days post fertilization (dpf) Tg(sqET20) larvae at 1, 3 and 5 hours post neomycin treatment, as well as from a non-treated control. Overall design: Transgenic zebrafish Tg(sqET20) larvae at 5 days post fertilization were exposed to neomycin, dissociated, and FACS sorted into GFP positive and GFP negative populations at 1, 3, and 5 hours following treatment, along with a mock treated 1 hr control. The experiment was performed in triplicate, for a total of 24 samples.
Gene-expression analysis of hair cell regeneration in the zebrafish lateral line.
No sample metadata fields
View SamplesRelative expression data from germinating seeds of Columbia (wt), the pkl mutant (pkl), Columbia plus uniconazole-P (Uwt) and the pkl-mutant plus uniconazole-P (Upkl).
The CHD3 remodeler PICKLE promotes trimethylation of histone H3 lysine 27.
No sample metadata fields
View SamplesPlant cells contain different O-acetylserine(thiol)lyase (OASTL) enzymes involved in Cys biosynthesis and located in different subcellular compartments. These enzymes are made up of a complex variety of isoforms resulting in different subcellular Cys pools. To unravel the contribution of cytosolic Cys to plant metabolism, we characterized the knockout oas-a1.1 and osa-a1.2 mutants, deficient in the most abundant cytosolic OASTL isoform in Arabidposis thaliana. Total intracellular Cys and glutathione concentrations were reduced, and the glutathione redox state was shifted in favour of its oxidized form. Interestingly, the capability of the mutants to chelate heavy metals did not differ from that of the wild type, but the mutants have an enhanced sensitivity to Cd. With the aim of establishing the metabolic network most influenced by the cytosolic Cys pool, we used the ATH1 GeneChip for evaluation of differentially expressed genes in the oas-a1.1 mutant grown under non-stress conditions. The transcriptomic footprints of mutant plants had predicted functions associated with various physiological responses that are dependent on reactive oxygen species and suggested that the mutant was oxidatively stressed. To further elucidate the specific function(s) of the OAS-A1 isoform in the adaptation response to cadmium we extended the trasncriptome experiment to the wild type and oas-a1.1 mutant plants exposed to Cd. The comparison of transcriptomic profiles showed a higher proportion of genes with altered expression in the mutant than in the wild type, highlighting up-regulated genes identified as of the general oxidative stress response rather than metal-responsive genes.
Knocking out cytosolic cysteine synthesis compromises the antioxidant capacity of the cytosol to maintain discrete concentrations of hydrogen peroxide in Arabidopsis.
Specimen part
View SamplesIn bacteria, the biosynthesis of cysteine is accomplished by two enzymes that are encoged by the cysK and cysM genes. CysM is also able to incorporate thiosulfate to produce S-sulfocysteine. In plant cells, the biosynthesis of cysteine occurs in the cytosol, mitochondria and chloroplasts. Chloroplasts contain two O-acetylserine(thiol)lyase homologs, which are encoded by the OAS-B and CS26 genes. An in vitro enzymatic analysis of the recombinant CS26 protein demonstrated that this isoform possesses S-sulfocysteine synthase activity and lacks O-acetylserine(thiol)lyase activity. In vivo functional analysis of this enzyme in knockout mutants demonstrated that mutation of cs26 suppressed the S-sulfocysteine synthase activity that was detected in wild type; furthermore, the mutants exhibited a growth phenotype, but penetrance depended on the light regime. The cs26 mutant plants also had reductions in chlorophyll content and photosynthetic activity (neither of which were observed in oas-b mutants), as well as elevated glutathione levels. However, cs26 leaves were not able to properly detoxify ROS, which accumulated to high levels under long-day growth conditions. The transcriptional profile of the cs26 mutant revealed that the mutation had a pleiotropic effect on many cellular and metabolic processes. Our finding reveals that S-sulfocysteine and the activity of S-sulfocysteine synthase play an important role in chloroplast function and are essential for light-dependent redox regulation within the chloroplast.
Arabidopsis S-sulfocysteine synthase activity is essential for chloroplast function and long-day light-dependent redox control.
No sample metadata fields
View SamplesHere we show using RNA-seq that cleavage by RNase E direct entry pervades in both the degradation and processing of RNA. We also give further evidence that direct entry is facilitated by cooperative interaction with segments in addition to the ones in which cleavage occurs. Overall design: RNA-seq profiles were compared between a temperature-sensitive mutant of rne and its congenic wild-type incubated at a non-permissive temperature. RNA seq profiles were also compared between samples before and after incubation with a 5''-sensing mutant of RNase E in vitro.
Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli.
Cell line, Subject
View SamplesTriple negative breast cancer (TNBC) represents a challenging tumor type due to their poor prognosis and limited treatment options. It is well recognize that clinical and molecular heterogeneity of TNBC is driven in part by mRNA and lncRNAs. To stratify TNBCs, we profiled mRNAs and lncRNA in 158 adjuvant TNBC tumors using an Affymetrix microarray platform. Lehmann clustering analysis allowed us to identify TNBC subtypes featuring unique lncRNA expression patterns, disease free and overall survival rates and particular gene ontology enrichments (performed with GSEA algorithm).
Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer.
Specimen part
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