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SRP072245
Mus musculus
282 Downloadable Samples
Illumina HiSeq 2000
Description
Previous 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
Publication Title
Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Mus musculus
- 57 Downloadable Samples
- Illumina HiSeq 2000
Description
We report a multi-omic study of sex differences and gene-by-sex interactions across a panel of 100 inbred strains of mice (the Hybrid Mouse Diversity Panel, HMDP), with a focus on metabolic and cardiovascular traits. For all traits examined, including obesity, insulin resistance, fatty liver, atherosclerosis, and gut microbiota composition, sex differences were influenced by genetic background. Loci identified by genome-wide association studies (GWAS) of the traits were frequently influenced by sex. Lyplal1, a gene implicated in human obesity, was shown to underlie a sex-specific locus for diet induced obesity. Many of the sex-dependent traits showed interdependencies as judged by correlation and shared gene expression patterns, indicating higher order regulation. Global gene expression analyses of tissues across the HMDP indicated that sex differences in mitochondrial functions in adipose contributed to many of the traits. Consistent with this, we observed that females tended to be more resistant to the adverse effects of a high fat diet, with smaller adipocytes and increased “browning” of white adipose tissue as compared to males. Sex-specific differences in mitochondrial activity were confirmed by examining respiration of isolated mitochondria. Gonadectomy experiments revealed thousands of genes influenced by sex hormones. In liver, a tissue exhibiting particularly strong differences in gene expression between tissues, sex hormones appeared to be the primary driver of the differences, whereas in adipose organizational effects of sex appeared to be more important. Overall design: Sixteen male and sixteen female C57BL/6J were purchased from The Jackson Laboratory (Bar Harbor). Mice were either maintained on a chow diet (Ralston Purina Company) or placed on an HF/HS diet (Research Diets D12266B) at 8 weeks of age until 16 weeks of age. At 6 weeks of age the mice were gonadectomized under isoflurane anesthesia. Scrotal regions of male mice were bilaterally incised, testes removed, and the incisions closed with wound clips. Ovaries of female mice were removed through an incision just below the rib cage. There were four mice per group. The muscle layer was sutured, and the incision closed with wound clips. In sham-operated control mice, incisions were made and closed as described above. The gonads were briefly manipulated, but remained intact. Gonadal fat and liver samples were taken for RNASeq expression profiling.
Publication Title
Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits.
Sample Metadata Fields
Sex, Age, Cell line, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
We used two RNA-Seq methods to measure the the global transcription levels in mouse liver cells. The data here provide insight into the pros and cons of whole transcript method and 3' RNA-Seq method. Overall design: KAPA (whole transcript method) and Lexogen (3' RNA-Seq method) were used to compare global expression in 6 mice of two conditions: 1) 3 normal diet mice 2) 3 iron-loaded diet mice.
Publication Title
A comparison between whole transcript and 3' RNA sequencing methods using Kapa and Lexogen library preparation methods.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following
Publication Title
An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hepatocellular carcinoma (HCC) is a highly prevalent and deadly disease world-wide. The survival of HCC patients is usually very poor due to the lack of efficient anti-cancer drugs
Publication Title
Synthesis and bio-molecular study of (+)-N-Acetyl-α-amino acid dehydroabietylamine derivative for the selective therapy of hepatocellular carcinoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Malignant mesothelioma (MM) is an asbestos-related malignancy and largely unresponsive to conventional chemotherapy or radiotherapy. Novel, more effective therapeutic strategies are needed for this fatal disease. We performed microarray analysis of MM using Affymetrix Human U133 Plus 2.0 array. Aberrant expression of the genes participating in semaphorin signaling were detected in malignant mesothelioma cells. All MM cells downregulated the expression of more than one gene for SEMA3B, 3F, and 3G when compared with Met5a, a normal pleura-derived cell line. In 12 of 14 epithelioid MM cells, the expression level of SEMA3A was lower than that in Met5a. An augmented expression of VEGFA was detected in half of the MM cells. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a and the non-epithelioid MMs. Next, gene expression profiling for the polycomb and trithorax group genes revealed that expression of BAP1, the catalytic subunit of the polycomb repressive deubiquitinase complex, and many trithorax group genes was downregulated in MMs compared with the expression of the same genes in Met5a cells. Perturbation of the polycombtrithorax balance plays a significant role in the pathogenesis of malignant mesothelioma.
Publication Title
Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disorder characterized by hamartomas of skin follicles, cystic lung disease, and renal neoplasia. Affected individuals carry heterozygous mutations in Folliculin (FLCN), a tumor suppressor gene that becomes biallelically inactivated in kidney tumors by second-hit mutations. Similar to other factors implicated in kidney malignancies, Folliculin has been shown to modulate activation of mammalian target of rapamycin (mTOR). However, its precise in vivo function is largely unknown because germline deletion of Flcn results in early embryonic lethality in animal models. We here describe mice deficient in the newly characterized Folliculin-Interacting Protein 1 (Fnip1). In contrast to Flcn, Fnip1-/- mice develop normally, are not susceptible to kidney neoplasia, but display a striking pro-B cell block that is independent of mTOR activity. We show that this developmental arrest results at least in part from impaired V(D)J recombination and caspase-induced cell death, and that pre-recombined V(D)J and Bcl2 transgenes reconstitute pre-B and mature B cell populations respectively. We also demonstrate that conditional deletion of Flcn recapitulates the pro-B cell arrest of Fnip1-/- mice. Our studies thus demonstrate that the Flcn-Fnip complex deregulated in BHD syndrome is absolutely required for B cell differentiation and that it functions both through mTOR dependent and independent pathways. Overall design: RNASeq data for two pro-B cell subsets (fraction B and CC'') isolated from wt and Fnip1-/- mice
Publication Title
The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
C57BL/6 mice were infected with the GS strain of G. duodenalis and total RNA prepared from the duodenum on day 10. Age matched controls were compared using Affy chips to determine changes in gene expression induced by infection.
Publication Title
Transcriptomic analysis of the host response to Giardia duodenalis infection reveals redundant mechanisms for parasite control.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 111 Downloadable Samples
- Illumina HiSeq 2000
Description
Alternative splicing and mRNA editing are known to contribute to transcriptome diversity. Although alternative splicing is pervasive and known to contribute to a variety of pathologies, including cancer, the genetic context for individual differences in isoform usage is still evolving. Similarly, although mRNA editing is ubiquitous and associated with important biological processes such as intracellular viral replication and cancer development, individual variations in and the genetic transmissibility of mRNA editing are equivocal. Here, we have used linkage analysis to show that both mRNA editing and alternative splicing are regulated by the macrophage genetic background and environmental cues. We show that distinct loci, potentially harboring variable splice factors, regulate the splicing of multiple transcripts. Additionally, we show that individual genetic variability at the Apobec1 locus results in differential rates of C-to-U(T) editing in murine macrophages; with mouse strains expressing mostly a truncated isoform of Apobec1 exhibiting lower rates of editing. As a proof of concept, we have used linkage analysis to identify 36 high confidence novel edited sites. These results provide a novel and complementary method that can be used to identify C-to-U editing sites in individuals segregating at specific loci and show that, beyond individual DNA sequence and structural changes, differential isoform usage and mRNA editing can contribute to intra-species genomic and phenotypic diversity. Overall design: Bone marrow derived macrophages (BMDM) from female AxB/BxA mice were left unstimulated or stimulated with IFNG/TNF, or CpG for 18 hrs or infected with infected with type II (Pru A7) for 8 hrs. The transcriptional response was then measured using the illumina RNA-seq protocol on an illumuna HiSeq 2000.
Publication Title
The genetic basis for individual differences in mRNA splicing and APOBEC1 editing activity in murine macrophages.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Analysis of the genes and cellular signalling cascades mediating the response of SCN slices to vasoactive intestinal peptide (VIP). Primary goal was to find novel genes that may be involved in circadian phase shifting for further study. Promoter analysis of significantly regulated genes and gene ontology analysis would provide information into pathways VIP acts through in the SCN.
Publication Title
Vasoactive intestinal peptide controls the suprachiasmatic circadian clock network via ERK1/2 and DUSP4 signalling.
Sample Metadata Fields
Specimen part
View Samples