Livers from 15 month old mice mainatined on one of 25 different diets varying in protein, carbohydrate, fat (P,C,F) and energy content were analysed. Energy content was categorised as low (8kJ/g), medium (13kJ/g) or high (17kJ/g) Mice were placed on diet from 3 weeks of age and a subset culled for various analyses. The rest of the cohort was allowed to live out their natural life to assess lifespan.
Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework.
Specimen part
View SamplesIncreasing evidence provide support that the mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, cell biology as well as of their role in the liver cell turnover and regeneration remain to be further clarified.
Isolation and characterization of a murine resident liver stem cell.
No sample metadata fields
View SamplesDuring each life cycle germ cells preserve and pass on both genetic and epigenetic information. In C. elegans, the ALG-3/4 Argonaute (AGO) proteins and their small-RNA cofactors are expressed during male gametogenesis and promote male fertility. Here we show that the CSR-1 AGO functions with ALG-3/4 to positively regulate target genes required for spermiogenesis. Our findings suggest that ALG-3/4 functions during spermatogenesis to amplify a small-RNA signal that represents an epigenetic memory of male-specific gene expression, while CSR-1, which is abundant in mature sperm, transmits this memory to offspring. Surprisingly, in addition to small RNAs targeting male-specific genes, we show that males also harbor an extensive repertoire of CSR-1 small RNAs targeting oogenesis-specific mRNAs. Together these findings suggest that C. elegans sperm transmit not only the genome but also epigenetic binary signals in the form of Argonaute/small-RNA complexes that constitute a memory of which genes were active in preceding generations. Overall design: Examine small RNA changes in WT and alg-3/4 mutant males cultured at 20°C and 25°C, as well as determine the small RNAs enriched in a FLAG::CSR-1 IP from male worms grown at 25°C. mRNA sequencing was also performed to determine how transcripts targeted by small RNAs change in mutant background at 20°C and 25°C.
Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part, Subject
View SamplesEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part
View SamplesWe present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the United States Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for sequence discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed, for these and qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcriptlevel profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.
A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium.
No sample metadata fields
View SamplesHuntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. We made induced pluripotent stem cell (iPSC) lines from HD patients and controls. Though no obvious effects of the CAG expansion on reprogramming or subsequent neural stem cell (NSC) production were seen, HD-NSCs showed CAG expansion-associated gene expression patterns and, upon differentiation, changes in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death for both medium and longer CAG repeat expansions, with some deficits greater in cells from longer repeat HD NSCs. The HD180 lines were more vulnerable than control lines to cellular stressors and BDNF withdrawal using a range of assays across consortium laboratories. This HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics.
Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.
Specimen part, Disease, Disease stage
View SamplesIn order to study parent-of-origin effects on gene expression, we performed RNAseq analysis (100bp single end reads) of 165 children who formed part of mother/father/child trios where genotype data was available from the HapMap and/or 1000 Genomes Projects. Based on phased genotypes at heterozygous SNP positions, we generated allelic counts for expression of the maternal and paternal alleles in each individual. This analysis reveals significant bias in the expression of the parental alleles for dozens of genes, including both previously known and novel imprinted transcripts. Overall design: This submission contains RNAseq data from 165 children from mother/father/child trios studied as part of the 1000 genomes and/or HapMap projects. We provide raw fastq format reads, and processed read counts per gene. Allelic count information can be provided by directly contacting the authors.
RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting.
Specimen part, Cell line, Subject
View SamplesWe performed whole-genome gene expression profiling in Pik3cg-/- mice and subsequent gene ontology clustering of differentially expressed genes compared to wild type mice, in order to investigate the role of Pik3cg in platelet membrane biogenesis and blood coagulation.
Maps of open chromatin guide the functional follow-up of genome-wide association signals: application to hematological traits.
Sex, Specimen part
View SamplesBleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signalling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes in our dataset – lips-15 – and confirmed that this reporter was expressed specifically in worms arrested at relatively low density. Finally, we show that conditioned media from high density L1 cultures was able to downregulate lips-15 even in L1 animals arrested at low density, and experiments using daf-22 mutant animals demonstrated that this effect is not mediated by the ascaroside family of signalling pheromones. Together, our data implicate a soluble signalling molecule in density sensing by L1 stage C. elegans, and provide guidance for design of experiments focused on early developmental gene regulation. Overall design: L1 Larvae arrested in M9 media at different densities were isolated for single L1 RNA-sequencing
Effects of Larval Density on Gene Regulation in <i>Caenorhabditis elegans</i> During Routine L1 Synchronization.
Cell line, Subject
View Samples