Lipid metabolic disarray in young and adult mice offspring's liver is induced by saturated fatty acids (SFA) but prevented by alpha linolenic acid (ALA, 18:3 3) in the maternal diet during pregnancy and lactation. The aim of the present study was to analyse the impact of maternal dietary ALA on the liver gene expression in the new-born offspring in comparison to a SFA diet. Methods: C57Bl6/J dams were fed with diets normal in calories but rich in ALA or SFA before mating and during pregnancy. Pups were sacrificed at birth and liver parameters were assessed. Gene expression was characterized by microarray analysis and validated by real time qPCR. Results: ALA compared to SFA in maternal diets during pregnancy, increased polyunsaturated fatty acids while differentially modified fatty acid desaturase activities in offspring liver. Overall, 474 and 662 genes from born pups liver, were differentially regulated by ALA and SFA compared to control diet (p<0.05; Fold change 2), respectively. Notably, Per3 was up-regulated by ALA whereas down-regulated by SFA, compared to control diet. Conclusions: ALA and SFA enriched diets differentially affect gene expression pattern in the offsprings liver. ALA in particular, upregulates genes associated to low adiposity.
Maternal Diet Enriched with α-Linolenic or Saturated Fatty Acids Differentially Regulates Gene Expression in the Liver of Mouse Offspring.
Specimen part, Disease, Treatment
View SamplesThe use of human pluripotent stem cells (hPSCs) in cell therapy is hindered by the tumorigenic risk from residual undifferentiated cells. Here we performed a high-throughput screen of over 52,000 small molecules, and identified 15 highly selective cytotoxic inhibitors of hPSCs (PluriSIns). Cellular and molecular analyses revealed that the most selective compound, PluriSIn #1, is a pluripotent-specific inhibitor of stearoyl-coA desaturase (SCD1), the key enzyme in the biosynthesis of monounsaturated fatty acids (MUFA). SCD1 inhibition in hPSCs induced ER stress, protein synthesis attenuation, and apoptosis of these cells, revealing that MUFA biosynthesis is crucial for their survival. PluriSIn #1 was also cytotoxic toward the ICM cells of mouse embryos, indicating that the dependence on SCD1 is inherent to the pluripotent state. Finally, application of PluriSIn #1 prevented teratoma formation from tumorigenic undifferentiated cells. Our novel method to eliminate undifferentiated cells from culture should thus increase the safety of hPSC-based treatments.
Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Sex, Specimen part, Treatment
View SamplesAnalysis of skeletal muscle gene expression from type 2 diabetic volunteers before and after 16 weeks of chronic exercise training (two groups, one undergoing aerobic ecercise and the other resistance training exercise)
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Specimen part
View SamplesOf the members of mitochondrial transcription termination factors (mTERFs) found in metazoans and plants known to regulate organellar gene expression at various levels, plant mTERF6 promotes maturation of a tRNA
Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.
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View SamplesGUN1 integrates retrograde signals in the chloroplast but the underlying mechanism is elusive. FUG1, a chloroplast translation initiation factor, and GUN1 are co-expressed at the transcript level, and FUG1 co-immunoprecipitates with GUN1. We used mutants of GUN1 (gun1-103) and FUG1 (fug1-3) to analyse their functional relationship at the physiological and systems-wide level, the latter including transcriptome and proteome analyses. Absence of GUN1 aggravates the effects of decreased FUG1 levels on chloroplast protein translation, resulting in transient additive phenotypes with respect to photosynthesis, leaf coloration, growth and cold acclimation. Variegation of the var2 mutant is enhanced by gun1-103 in terms of increasing the fraction of white sectors, in contrast to fug1-3 that acts as suppressor. The transcriptomes of fug1-3 and gun1-103 are very similar, but absence of GUN1 alone has almost no effects on protein levels, whereas chloroplast protein accumulation is markedly decreased in fug1-3. In gun1 fug1 double mutants, effects on transcriptomes and particularly proteomes are enhanced. Our results show that GUN1 function becomes critical when chloroplast proteostasis is perturbed by decreased translation (fug1) or degradation (var2) of chloroplast proteins. The functions of FUG1 and GUN1 appear to be related, corroborating the view that GUN1 operates in chloroplast proteostasis. Overall design: Examination of differential gene expression in the Arabdidopsis thaliana gun1, fug1 and gun1 fug1 mutants compared to wild type in three replicates
Relationship of GUN1 to FUG1 in chloroplast protein homeostasis.
Subject
View SamplesChanges ins organellar gene expression trigger retrograde signalling. Prolyl-tRNA synthetase (PRORS1) is located in chloroplasts and mitochondria. Thus, prors1-2 mutants are impaired in chloroplast and mitochondrial gene expression.
Identification of target genes and transcription factors implicated in translation-dependent retrograde signaling in Arabidopsis.
Age, Specimen part
View SamplesThe in vitro test battery of the European research consortium ESNATS (novel stem cell-based test systems) has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/ dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test.
Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration.
Sex, Specimen part
View SamplesHigh-density kinetic analysis of the metabolomic and transcriptomic response of Arabidopsis to temperature and light
High-density kinetic analysis of the metabolomic and transcriptomic response of Arabidopsis to eight environmental conditions.
Specimen part, Time
View SamplesComparison of expression of Arabidopsis thaliana Col-0 and T-DNA insertion line of RAP2.4a under time dependent light stress by transfer to high light
Meta-analysis of retrograde signaling in Arabidopsis thaliana reveals a core module of genes embedded in complex cellular signaling networks.
Specimen part
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