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SRP127547
Homo sapiens
21 Downloadable Samples
NextSeq 500
Description
Matching sets of RfxCasR and shRNAs targeting ANXA4 and B4GALNT1 plus non-targeting (NT) controls were profiled by mRNA sequencing to compare non-specific transcriptome perturbations for both shRNA and RfxCasR technologies. Overall design: Three biological replicates for 3 shRNAs and 2 RfxCasR guide RNAs plus 2 RfxCasR arrays expresssed in HEK 293FT cells
Publication Title
Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance.
Publication Title
PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity.
Sample Metadata Fields
Sex, Age, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Polyphenolic compounds, such as resveratrol, have recently received widespread interest due to their ability to mimic effects of calorie restriction. The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology and underlying processes. Nine healthy obese men were supplemented with placebo and 150mg/day resveratrol for 30 days, separated by a 4-week washout period. A postprandial abdominal subcutaneous adipose tissue biopsy was collected to assess adipose tissue morphology and gene expression using microarray analysis. Resveratrol significantly decreased adipocyte size, with a shift towards a reduction in the proportion of large and very large adipocytes and an increase in small adipocytes. Microarray analysis revealed downregulation of Wnt, Notch and BMP/TGF- signaling pathways and upregulation of pathways involved in cell cycle after resveratrol supplementation, suggesting enhanced adipogenesis. Furthermore, the lysosomal/phagosomal pathway and the transcription factor EB were upregulated, reflecting an alternative pathway of lipid breakdown by autophagy. These data suggest that adipose tissue is an important target tissue for the effects of resveratrol in humans, but further research is necessary to investigate whether it translates into an improved adipose tissue function.
Publication Title
The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Race, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Activation of the STING (Stimulator of Interferon Genes) pathway by microbial or self-DNA, as well as cyclic di nucleotides (CDN), results in the induction of numerous genes that suppress pathogen replication and facilitate adaptive immunity. However, sustained gene transcription is rigidly prevented to avoid lethal STING-dependent pro-inflammatory disease by mechanisms that remain unknown. We demonstrate here that after autophagy-dependent STING delivery of TBK1 (TANK-binding kinase 1) to endosomal/lysosomal compartments and activation of transcription factors IRF3 (interferon regulatory factors 3) and NF-B (nuclear factor kappa beta), that STING is subsequently phosphorylated by serine/threonine UNC-51-like kinase (ULK1/ATG1) and IRF3 function is suppressed. ULK1 activation occurred following disassociation from its repressor adenine monophosphate activated protein kinase (AMPK), and was elicited by CDNS generated by the cGAMP synthase, cGAS. Thus, while CDNs may initially facilitate STING function, they subsequently trigger negative-feedback control of STING activity, thus preventing the persistent transcription of innate immune genes.
Publication Title
Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The genome of vertebrates contains endogenous retroviruses (ERVs) that have resulted from ancestral infections by exogenous retroviruses. ERVs are germline encoded, transmitted in a Mendelian fashion and account for about 8% of the human and 9.9% of the murine genome, respectively1, 2. By spontaneous activation and reintegration ERVs may cause insertional mutagenesis and thus participate in the process of malignant transformation or progression of tumor growth3, 4. However, if the innate immune system is able to recognize and control ERVs has not yet been elucidated. Here we report that, in vitro, nucleic-acid sensing TLRs on dendritic cells are activated by retroviral RNA and DNA from infected cells in vitro. Infection of TLR competent wild type mice with murine leukemia virus (MuLV)-like ERV isolates results in non-canonical gene upregulation, independent of type I IFN. In vivo, TLR3, -7 and -9 triple deficient mice (TLR379-/-) and mice with non functional TLR3, 7 and 9 signaling due to a mutation in UNC93B develop spontaneous ERV-induced viremia. More importantly, in TLR379-/- mice ERV-induced viremia correlates with acute T cell lymphoblastic leukemia (T-ALL). Multiple independent TLR379-/- T cell leukemia lines produce infectious MuLV of endogenous origin. These cell lines display de novo retroviral integration into the Nup214 or Notch1 gene locus leading to gene dysregulation that is reminiscent of aberrant Nup214 and Notch1 expression in human T-ALLs5. Overall, our results demonstrate that in addition to their role in innate immune defense against exogenous pathogens, TLR3,-7, and -9 may be essential for the control of endogenous retroviral mediated T-cell lymphomagenesis.
Publication Title
Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 3000
Description
The challenge of predicting which patients with breast cancer will develop metastases leads to the overtreatment of patients with benign disease and to the inadequate treatment of the aggressive cancers. Here, we report the development and testing of a microfluidic assay that quantifies the abundance and proliferation of migratory cells in breast-cancer specimens, for the assessment of their metastatic propensity and for the rapid screening of potential antimetastatic therapeutics. On the basis of the key roles of cell motility and proliferation in cancer metastasis, the device accurately predicts the metastatic potential of breast-cancer cell lines and of patient-derived xenografts. Compared to unsorted cancer cells, highly motile cells isolated by the device exhibited similar tumourigenic potential but markedly increased metastatic propensity in vivo. RNA sequencing of the highly motile cells revealed an enrichment of motility-related and survival-related genes. The approach might be developed into a companion assay for the prediction of metastasis in patients and for the selection of effective therapeutic regimens. Overall design: RNA was isolated from samples of 1000Â migratory or unsorted cells in triplicate
Publication Title
A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 133 Downloadable Samples
- NextSeq 500
Description
The mammalian genome contains thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to play critical roles in diverse cellular processes through a variety of mechanisms. While some lncRNA loci encode RNAs that act non-locally (in trans), emerging evidence indicates that many lncRNA loci act locally (in cis) to regulate expression of nearby genes—for example, through functions of the lncRNA promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms. To address these challenges, we developed a genome-scale CRISPR-Cas9 activation screen targeting more than 10,000 lncRNA transcriptional start sites (TSSs) to identify noncoding loci that influence a phenotype of interest. We found 11 novel lncRNA loci that, upon recruitment of an activator, each mediate BRAF inhibitor resistance in melanoma. Most candidate loci appear to regulate nearby genes. Detailed analysis of one candidate, termed EMICERI, revealed that its transcriptional activation results in dosage-dependent activation of four neighboring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a CRISPR toolkit to systematically discover functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function. Overall design: RNA-seq on A375 cells overexpressing candidate lncRNA or protein-coding gene.
Publication Title
Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
RNA-seq and ATAC-seq data to understand how gene regulation and chromatin accessibility correlates with function enrichment in CRISPR screen for melanoma drug resistance
Publication Title
Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We performed a microarray experiment to assess SAHA-induced changes in expression of genes of the homologous recombination DNA repair pathway
Publication Title
Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inflammation-driven carcinogenesis is mediated through STING.
Sample Metadata Fields
Specimen part
View Samples