We identified miR-95 in a screen for miRNAs which functionally affect
A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder.
Cell line
View SamplesIdentify genes in the aorta whose expressions under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HDMP is comprised of classical inbred and recombinant inbred wild-type mice. The RMA values of genes were used for genome-wide association as described in Bennett et al. Genome Research 2010 (PMID 20054062). These data were used to identify candidate genes at loci associated with atherosclerosis.
High-resolution association mapping of atherosclerosis loci in mice.
Sex, Age, Specimen part
View SamplesLinkage analysis of complex traits in mice is a powerful tool to find loci affecting the phenotype but it has a poor resolution making it difficult to identify the underlying genes. We show here, using whole genome association analysis of gene expression traits in an outbred mouse population, the MF1 stock, that mapping resolution is greatly increased as compared to linkage. The fact that eQTLs discovered in other crosses were replicated and successfully mapped with high resolution in this population provides a strong proof of concept. In addition, we show that this population is a useful resource to resolve the eQTL hotspots detected in other studies. Finally, we highlight the importance of correcting for population structure in whole genome association studies in the outbred stock.
High-resolution mapping of gene expression using association in an outbred mouse stock.
No sample metadata fields
View SamplesAbstract: The LXR and SREBP transcription factors are key regulators of cellular and systemic cholesterol homeostasis. The molecular mechanisms that integrate these pathways are incompletely understood. Here we show that ligand activation of LXRs in liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as an unexpected mediator of this effect. LeXis is robustly induced in mouse liver in response to western diet feeding or pharmacologic LXR activation. Expression of LeXis in liver inhibits cholesterol biosynthesis and lowers plasma cholesterol levels. Reciprocally, knockdown of LeXis increases hepatic cholesterol content and raises plasma cholesterol levels. LeXis interacts with the heterogeneous nuclear ribonucleoprotein Raly and regulates its binding to cholesterol biosynthetic gene promoters. These studies outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms orchestrating systemic sterol homeostasis. Overall design: Global RNA expression from primary hepatocytes treated with or without GW3965 were compared by RNA-Seq.
Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.
Specimen part, Subject
View SamplesPrevious studies had shown that integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL "hotspots" associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provides a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation. Overall design: 282 samples, 3 biological replicates per strain
Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
Sex, Cell line, Subject
View SamplesWe report the effects of Rapamycin treatment on the transcriptome of normal human dermal fibroblasts isolated from foreskin (designated 2DD). We sequenced mRNA from 2 replicates of proliferative (PRO) quiescent (QUI, serum starved) or treated with 500nM Rapamycin for 5 days (RAP). Comparative analyses with PRO transcripts a baseline indicate that genes that changed expression from Rapamycin treated fibroblasts are significantly different from those of quiescence cells. Rapamycin treated cells showed a significant enrichment for cytokines from the Il-6 cascade. Overall design: Examination of mRNAs from proliferative, quiescent (serum starvation) and Rapamycin (5oonM, 5days) treated 2DD normal human dermal/foreskin fibroblasts.
Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts.
No sample metadata fields
View SamplesWe analyzed the global effect of c-Myb knockdown by sequencing the transcriptomes of K-562 cells transfected with control siRNA and si2992 (MYB knockdown), as well as K-562 cells stably expressing TY-tagged wild type c-Myb and c-Myb D152V transfected with si2992 Overall design: Cells were tranfected with siRNA and 24 hours after total RNA was extracted. Three individual experiments were performed. Libraries were prepared and 125-bp paired-end reads were obtained using an Illumina HiSeq 2500 sequencer
A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function.
Specimen part, Cell line, Subject
View SamplesMicroarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)
Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.
Specimen part
View SamplesImmortalized colonic epithelial progenitor cells derived from normal human colon biopsies express stem cell markers and differentiate in vitro
Immortalized epithelial cells derived from human colon biopsies express stem cell markers and differentiate in vitro.
Sex, Age, Specimen part
View SamplesNovel, systems-based approach to mouse genetics.
A high-resolution association mapping panel for the dissection of complex traits in mice.
Specimen part
View Samples