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SRP074380
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- Bos taurus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Bovine papillomavirus (BPV) is the causative agent of papillomatosis in cattle. The disease causes cutaneous and mucosal lesions that can be minimized or lead to the appearance of malignant tumors. This study aims to identify possible molecular mechanisms that are behind the pathological processes associated with bovine papillomatosis through the identification of genes related to the development of the lesions. For this, next-generation RNA sequencing was used to assess differentially expressed genes in infected by BPV and non-infected bovines. Three animals with papillomatosis lesion and three without papillomatosis lesion were studied. The Galaxy platform was used to analyze the data generated by the sequencing. The Illumina output files were converted to FASTQ format. Quality evaluation was performed using FastQC and the sequence quality cut was performed using Trimmomatic. TopHat and Bowtie were used to map and align the reads with the reference genome. The abundance of the expressed genes was verified using Cuffilinks. Cuffdiff was used for differential expression analysis. Functional annotation of the differentially expressed genes was performed using Gene Ontology (GO) databases. RNA-sequencing generated a total of 121,722,238 of reads. In the gene expression analysis, a total of 13,421 genes expressed were identified and of these 1343 were differentially expressed. The functional annotation of differentially significant genes showed that many genes presented functions or they were related to metabolic pathways associated with the progression of papillomatosis lesions and cancer development in cattle. Although more studies are needed, this is the first study that focused on a large-scale evaluation of gene expression associated with the BPV infection, which is important to identify possible mechanisms regulated by the host genes that are necessary the development of the lesion Overall design: Analysis of three BPV infected and three BPV non-infected samples
Publication Title
Comparative transcriptomic analysis of bovine papillomatosis.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Rattus norvegicus
- 11 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Publication Title
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Rationale. Lung inflammation in premature infants contributes to development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without apparent adverse effects as occur with systemic dexamethasone therapy. Objectives. To determine effects of budesonide on differential genes expression in human fetal lung Overall design: Methods. We prepared RNA from 3 samples of human fetal lung at 23 weeks gestation before (preculture, PC) and after 4 days culture as explants with (Bud) or without (Way) budesonide (30 nM) and performed RNAseq on the 9 samples.
Publication Title
Antiinflammatory Effects of Budesonide in Human Fetal Lung.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
Publication Title
Genomic analysis of reactive astrogliosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We analyze the contribution of alternative splicing to the transcriptional complexity in adipose tissue and the development of diet-induced obesity. Overall design: We use Next generation sequencing analysis of eWAT from control and Nova1 and Nova2-deficient mice fed with a control diet
Publication Title
An alternative splicing program promotes adipose tissue thermogenesis.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Astrogliosis is a hallmark of the response to brain ischemia, comprised of changes in gene expression and morphology. Hsp72 protects from cerebral ischemia, and although several mechanisms of protection have been investigated, effects on astrocyte activation are unknown. To identify potential mechanisms of protection, gene expression was assessed in mice subjected to middle cerebral artery (MCAO) or sham surgery, of either wildtype (WT) or Hsp72-overexpressing (Hsp72Tg) mice. After stroke, both genotypes exhibited genes related to cell death, stress response, and immune response. Furthermore, genes indicative of astrocyte activation, including cytoskeletal proteins and cytokines, were upregulated. To measure astrocyte activation after stroke, detailed histological and morphological analyses were performed in the cortical penumbra after stroke using unbiased stereology. Consistent with other reports, we observed a marked and persistent increase in glial fibrillary acidic protein (GFAP ) as soon as 3 hours after MCAO. In contrast, vimentin immunoreactivity appeared 12-24 hours after stroke, peaked at 72 hours, and returned to baseline after 30 days. Surprisingly, no change in overall astrocyte number was observed based on glutamine synthetase (GS) immunoreactivity. To determine if Hsp72Tg mice exhibited altered astrocyte activation compared to WT controls, morphological evaluation by fractal analysis was used. Overexpression of Hsp72 reduced astrocyte cell area, arbor area, and to a lesser extent fractal dimension, 72 hours following stroke. In conclusion, in vivo overexpression of Hsp72 alters gene expression following stroke, including genes involved in astrocyte activation, and decreases astrocyte activation acutely following MCAO. Thus, modulation of astrogliosis may be a neuroprotective mechanism exerted by Hsp72 after ischemia.
Publication Title
Effects of heat shock protein 72 (Hsp72) on evolution of astrocyte activation following stroke in the mouse.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 4000
Description
The development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Publication Title
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We performed a factorial experiment examining the effects of calorie restriction (CR) and exercise (EX) in mice. CR mice received 70% of calories but 100% of all other nutrients compared to AL mice. Food consumption, weight gain, and physical activity levels were recorded for 6 weeks.
Publication Title
Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.
Sample Metadata Fields
No sample metadata fields
View Samples