We report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait. Overall design: Examination of the expression profile of mice adipose tissues fed either standard (Std), High-fat/high-sucrose (HF/HS) or HF/HS + antioxidant formulation (AOF) for 180 days
Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract.
Age, Specimen part, Cell line, Subject
View SamplesBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological. We used transcriptomic analysis to investigate LXR pathway, and cholesterol metabolism in leukemic cells. Malignancy with a poor prognosis that derives from plasmacytoid dendritic cells (PDC). No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared to those of acute myeloid leukemia (AML) and T-acute lymphoblastic leukemia (T-ALL), as well as the transcriptomic signature of primary PDC. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of ATP Binding Cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with three signaling pathways associated with leukemic cell survival, namely: NF-B activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor IL-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with an increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.
LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis.
Specimen part, Disease, Disease stage
View SamplesDREAM (downstream regulatory element antagonist modulator) is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. Previous studies have shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger3 (NCX3) in cerebellar granules to control Ca2+ homeostasis and survival of these neurons. To achieve a more global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Our results indicate that DREAM is a major transcription factor in the cerebellum that regulates genes important for cerebellar development.
Reduced Mid1 Expression and Delayed Neuromotor Development in daDREAM Transgenic Mice.
Specimen part
View SamplesDominant gain-of-function alleles of Arabidopsis phytochrome B were recently shown to confer light-independent, constitutive photomorphogenic (cop) phenotypes to transgenic plants (Su & Lagarias 2007 Plant Cell 19, 2124-2139). In the present study, comparative transcript profiling experiments were performed to assess whether the pattern of gene expression regulated by these alleles accurately reflects the process of photomorphogenesis in wild-type Arabidopsis. Whole genome transcriptional profiles of dark-grown phyAphyB seedlings expressing the Y276H mutant of phyB (YHB) revealed that YHB reprograms about 13% of the Arabidopsis transcriptome in a light-independent manner. The YHB-regulated transcriptome proved qualitatively similar to, but quantitatively greater than those of wild-type seedlings grown under 15 or 50 umol m-2 m-1 continuous red light (Rc). Among the 2977 genes statistically significant two-fold (SSTF) regulated by YHB in the absence of light include those encoding components of the photosynthetic apparatus, tetrapyrrole/pigment biosynthetic pathways and early light-responsive signaling factors. Approximately 80% of genes SSTF regulated by Rc were also YHB-modulated. Expression of a notable subset of 346 YHB-regulated genes proved to be strongly attenuated by Rc, indicating compensating regulation by phyC-E and/or other Rc-dependent processes. Since the majority of these 346 genes are regulated by the circadian clock, these results suggest that phyA- and phyB-independent light signaling pathway(s) strongly influence clock output. Together with the unique plastid morphology of dark-grown YHB seedlings, these analyses indicate that the YHB mutant induces constitutive photomorphogenesis via faithful reconstruction of phyB signaling pathways in a light-independent fashion.
A light-independent allele of phytochrome B faithfully recapitulates photomorphogenic transcriptional networks.
No sample metadata fields
View SamplesBackground and Aims: Gene expression analysis of colon biopsies using high-density oligonucleotide microarray can contribute to the understanding of local pathophysiological alterations and to functional classification of precancerous adenoma, different stage colorectal carcinomas (CRC) and inflammatory bowel diseases (IBD).
Evaluation of microarray preprocessing algorithms based on concordance with RT-PCR in clinical samples.
No sample metadata fields
View SamplesNatural grape-juice fermentations involve the sequential development of different yeast species which strongly influence the chemical and sensorial traits of the final product. In the present study,we aimed to examine the transcriptomic response of Saccharomyces cerevisiae to the presence of Hanseniaspora guilliermondii wine fermentation.
Genomic expression program of Saccharomyces cerevisiae along a mixed-culture wine fermentation with Hanseniaspora guilliermondii.
Treatment, Time
View SamplesThe intestine is composed of an epithelial layer, containing rapidly proliferating cells that mature into two distinct anatomic regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for the whole intestine, no studies have compared stem cells derived from the small and large intestine. Here, we report intrinsic differences between these two populations of cells. Primary epithelial cells isolated from human fetal small and large intestine and expanded with Wnt agonist, R-spondin 2, displayed differential expression of stem cell markers and separate hierarchical clustering of gene expression involved in differentiation, proliferation and disease pathways. Using a three-dimensional in vitro differentiation assay, single cells derived from small and large intestine formed distinct organoid architecture with cellular hierarchy similar to that found in primary tissue. Our characterization of human fetal intestinal stem cells defies the classical definition proposed by most where small and large intestine are repopulated by an identical epithelial stem cell and raises the question of the importance of intrinsic and extrinsic cues in the development of intestinal diseases.
Distinct human stem cell populations in small and large intestine.
Specimen part
View SamplesPlants aquire nitrogen from the soil, most commonly in the form of either nitrate or ammonium. Unlike ammonium, nitrate must be reduced (with NADH and ferredoxin as electron donors) prior to assimilation. Thus, nitrate nutrition imposes a substantially greater energetic cost than ammonium nutrition. Our goal was to compare the transcriptomes of nitrate-supplied and ammonium-supplied plants, with a particular interest in characterizing the differences in redox metabolism elicited by different forms of inorganic nitrogen.
Distinct signalling pathways and transcriptome response signatures differentiate ammonium- and nitrate-supplied plants.
Specimen part
View SamplesKaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognizable by its distinctive red skin lesions. The lesions are KSHV infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. Here we examine KSHVs modulation of Notch signaling using wild-type LEC cells co-cultured with DLL4 and JAG1 expressing LEC cells.
KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia.
No sample metadata fields
View SamplesBackground The RNA steady-state levels in the cell are a balance between synthesis and degradation rates. Although transcription is important, RNA processing and turnover are also key factors in the regulation of gene expression. In Escherichia coli there are three main exoribonucleases (RNase II, RNase R and PNPase) involved in RNA degradation. Although there are many studies about these exoribonucleases not much is known about their global effect in the transcriptome. Results In order to study the effects of the exoribonucleases on the transcriptome, we sequenced the total RNA (RNA-Seq) from wild-type cells and from mutants for each of the exoribonucleases (?rnb, ?rnr and ?pnp). We compared each of the mutant transcriptome with the wild-type to determine the global effects of the deletion of each exoribonucleases in exponential phase. We determined that the deletion of RNase II significantly affected 187 transcripts, while deletion of RNase R affects 202 transcripts and deletion of PNPase affected 226 transcripts. Surprisingly, many of the transcripts are actually down-regulated in the exoribonuclease mutants when compared to the wild-type control. The results obtained from the transcriptomic analysis pointed to the fact that these enzymes were changing the expression of genes related with flagellum assembly, motility and biofilm formation. The three exoribonucleases affected some stable RNAs, but PNPase was the main exoribonuclease affecting this class of RNAs. We confirmed by qPCR some fold-change values obtained from the RNA-Seq data, we also observed that all the exoribonuclease mutants were significantly less motile than the wild-type cells. Additionally, RNase II and RNase R mutants were shown to produce more biofilm than the wild-type control while the PNPase mutant did not form biofilms. Conclusions In this work we demonstrate how deep sequencing can be used to discover new and relevant functions of the exoribonucleases. We were able to obtain valuable information about the transcripts affected by each of the exoribonucleases and compare the roles of the three enzymes. Our results show that the three exoribonucleases affect cell motility and biofilm formation that are two very important factors for cell survival, especially for pathogenic cells. Overall design: RNA-Seq of E. coli K-12 MG1693 wild-type(wt) and three exoribonucleases mutants was done with Illumina Hi-Seq platform.
PNPase is involved in the coordination of mRNA degradation and expression in stationary phase cells of Escherichia coli.
Cell line, Subject
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