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E-MEXP-1135
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
12 C57BL/6 mice were infected orogastrically with the H. pylori strain SS1. After 6 and 12 months, 3 non-infected and 3 infected mice were sacrificed and stomachs isolated. Gastric tissues were disaggregated and total RNA were isolated by TRIzol extraction and then purified on RNeasy minicolumns. After synthesis of the first cDNA strand (In vitrogen), the double-stranded cDNA was obtained and used to produce biotin-labeled cRNA (Enzo Diagnostic). FRagmented cRNA was hybridized to GeneChip Mouse expression array 430A (Affymetrix).
Publication Title
Interferon gamma-signature transcript profiling and IL-23 upregulation in response to Helicobacter pylori infection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Abstract: Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assess the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community to lack a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria show increased susceptibility to metabolic disease. Furthermore, bacterially-induced reduction of methyl-donor availability alters global DNA methylation patterns in both adult mice and their offspring in utero and engenders anxious behavior. Altogether, our results reveal an underappreciated aspect of bacterial choline metabolism (i.e., methyl-donor depletion) that is linked to alterations in metabolism, epigenetics, and behavior. More broadly, this work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal levels of nutrient intake. Overall design: 8 samples in total (biological n=4 per for each defined community; 9kw old female C57BL/6 mouse liver; 2 weeks of colonization and maintenance on 1% choline diet; 4hours of fasting prior to sacrifice)
Publication Title
Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Abstract: Histones are small proteins that form the core of nucleosomes, around which eukaryotic DNA wraps to ultimately form the highly organized and compressed structure known as chromatin. The N-terminal tails of histones are highly modified, and the modification state of these proteins dictates whether chromatin is permissive or repressive to processes that require physical access to DNA, including transcription and DNA replication and repair. The enzymes that add and remove histone modifications are known to be exquisitely sensitive to endogenous small molecule metabolite availability. In this manner, chromatin can adapt to changes in environment, particularly diet-induced metabolic state. Importantly, gut microbiota contribute to robust host metabolic phenotypes, and produce a myriad of metabolites that are detectable in host circulation. Further, gut microbial community composition and metabolite production are regulated by host diet, as a major source of carbon and energy for the microbiota. While prior studies have reported robust host metabolic associations with gut microbiota, the mechanisms therein remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues including colon, adipose tissue, and liver. This regulatory relationship is altered by diet: a “Western-type” diet leads to a general suppression of the microbiota-dependent chromatin changes observed in a polysaccharide rich diet. Finally, we demonstrate that supplementation of germ-free mice with major products of gut bacterial fermentation (i.e., short-chain fatty acids acetate, propionate, and butyrate) is sufficient to recapitulate many of the effects of colonization on host epigenetic states. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health. Overall design: 15 samples in total (biological n=3 per for each of 5 conditions; 19kw old male C57BL/6J mouse liver): (1) GF mouse liver on chow diet, (2) ConvR mouse liver on chow diet, (3) ConvD mouse liver on chow diet, (4) GF mouse liver on HF/HS diet, (5) ConvR mouse liver on HF/HS diet
Publication Title
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Abstract: Histones are small proteins that form the core of nucleosomes, around which eukaryotic DNA wraps to ultimately form the highly organized and compressed structure known as chromatin. The N-terminal tails of histones are highly modified, and the modification state of these proteins dictates whether chromatin is permissive or repressive to processes that require physical access to DNA, including transcription and DNA replication and repair. The enzymes that add and remove histone modifications are known to be exquisitely sensitive to endogenous small molecule metabolite availability. In this manner, chromatin can adapt to changes in environment, particularly diet-induced metabolic state. Importantly, gut microbiota contribute to robust host metabolic phenotypes, and produce a myriad of metabolites that are detectable in host circulation. Further, gut microbial community composition and metabolite production are regulated by host diet, as a major source of carbon and energy for the microbiota. While prior studies have reported robust host metabolic associations with gut microbiota, the mechanisms therein remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues including colon, adipose tissue, and liver. This regulatory relationship is altered by diet: a “Western-type” diet leads to a general suppression of the microbiota-dependent chromatin changes observed in a polysaccharide rich diet. Finally, we demonstrate that supplementation of germ-free mice with major products of gut bacterial fermentation (i.e., short-chain fatty acids acetate, propionate, and butyrate) is sufficient to recapitulate many of the effects of colonization on host epigenetic states. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health. Overall design: 9 samples in total (biological n=3 per for each of 3 conditions; 14kw old male C57BL/6J mouse liver): (1) GF mouse liver on chow diet, (2) ConvD mouse liver on chow diet, (3) GF mouse liver on chow diet + supplemented drinking water with short chain fatty acids
Publication Title
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Humans with metabolic and inflammatory diseases frequently harbor lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Results: We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary components to (i) impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization, (ii) improve intestinal barrier function, (iii) lower systemic inflammation and (iv) ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate improves gut barrier function and reduces atherosclerosis development. Conclusions: Altogether, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis. Overall design: Intestinal mRNA profiles of gnotobiotic ApoE KO mice colonized with "core" community or "core plus Roseburia intestinalis" were generated by deep sequencing using Illumina HiSeq.
Publication Title
Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MORAB-003 significantly upregulated a number of genes involved in autophagic processing, including GABARAPL2, LC3II (MAP1LC3B), ATG3, ATG4B, and BECN1, while expression of the oncogenic factor PIK3C3 was downregulated.
Publication Title
Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression data obtained from induced pluripotent stem cells derived from wild type fibroblasts (iPSc WT) and from Gaucher Disease type 2 fibroblasts (GD iPSc). Also, gene expression analysis from the initial fibroblasts was made (WT fibroblasts and GD- fibroblasts), as well as gene expression analysis from a human embryonic stem cell line (hES4).
Publication Title
Neuronopathic Gaucher's disease: induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify the gene signature accounting for the distinct clinical outcomes in ovarian clear cell cancer patients
Publication Title
Identification of novel therapeutic targets in microdissected clear cell ovarian cancers.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa pao1
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Although Pseudomonas aeruginosa is an opportunistic pathogen that does not often naturally infect alternate hosts such as plants, the plant-P. aeruginosa model has become a widely recognized system for identifying new virulence determinants and studying pathogenesis of this organism. Here we examine how both host factors and P. aeruginosa PAO1 gene expression are affected in planta after infiltration into incompatible and compatible cultivars of tobacco (Nicotiana tabacum L.) Nicotiana tabacum has a resistance gene (N) against tobacco mosaic virus; and although resistance to PAO1 infection correlated to the presence of a dominant N-gene, our data suggests that it is not a factor in resistance against Pseudomonas. We did observe that the resistant tobacco cultivar had higher basal levels of salicylic acid, and a stronger salicylic acid response upon infiltration of PAO1. Salicylic acid acts as a signal to activate defense responses in plants, limiting the spread of the pathogen and preventng access to nutrients. It has also been shown to have direct virulence modulating effects on P. aeruginosa. We also examined host effects on the pathogen by analyzing global gene expression profiles of bacteria removed from the intracellular fluid of the two plant hosts. We discovered that the availability of micronutrients, particularly sulfate and Pi, are important factors in in planta pathogenesis, and that the amounts of these nutrients made available to the bacteria may in turn have an effect on virulence gene expression. Indeed, there are several reports suggesting that P. aeruginosa virulence is influenced in mammalian hosts by the availability of iron and by levels of O2.
Publication Title
Global gene expression profiles suggest an important role for nutrient acquisition in early pathogenesis in a plant model of Pseudomonas aeruginosa infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The essential thiol antioxidant, glutathione (GSH) is recruited into the nucleus of mammalian cells early in cell proliferation, suggesting a key role of the nuclear thiol pool in cell cycle regulation. However, the functions of nuclear GSH (GSHn) and its integration with the cytoplasmic GSH (GSHc) pools in whole cell redox homeostasis and signaling are unknown. Here we show that GSH is recruited into the nucleus early in cell proliferation in Arabidopsis thaliana, confirming the requirement for localization of GSH in the nucleus as a universal feature of cell cycle regulation.
Publication Title
Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield.
Sample Metadata Fields
Treatment
View Samples