SNPs affecting disease risk often reside in non-coding genomic regions. Here we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPAR?, a nuclear receptor for antidiabetic drugs. Many such SNPs alter binding motifs for PPAR? or cooperating factors, and functionally regulate nearby genes whose expression is strain-selective and imbalanced in heterozygous F1 mice. Moreover, genetically-determined binding of PPAR? accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof-of- concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPAR? binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome- wide association studies. One PPAR? motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPAR? genomic occupancy determines individual disease risk and drug response. Overall design: Comparison of 5 RNA-seq experiments between 2 strains of mice differing in diet and fat depot. One of the experiments was evaluation of the response to a drug Rosiglitazone. Our RNA-seq data comprises primarily of 4 main experiments: The first experiment consists of samples taken from 2 strains of mice and their F1 progeny The samples are all taken from the same depot and when the mice were fed the same chow diet The second experiment has 2 parts, the first one involves samples taken from the 2 strains from the same eWAT depot when they were kept on a Low Fat Diet (LFD) This first part serves as a control for the second one in which the mice were treated with a drug, rosiglitazone in conjunction with a LFD The third experiment consists of samples taken from mice being fed on LFD. The samples are taken from the eWAT depot for both the strains. The fourth experiment consists of samples taken from mice being fed on LFD. The samples are taken from the iWAT depot for both the strains. We also have a solitary sample from a GRO-seq experiment which was done on eWAT in a B6 strain of mice being fed a LFD eWAT: epididymal White Adipose Tissue iWAT: inguinal White Adipose Tissue LFD-12w: mice were fed a control low fat diet (Research Diet D12450B) chow: mice were fed standard rodent chow Diet LFD w/rosiglitazone: Drug rosiglitazone (Cayman Chemicals) was incorporated into low fat diet D12450B by Research Diets at 36mg/kg of diet. Mice received control low fat diet for 10 weeks (age 6-16 weeks), and the rosiglitazone-containing diet versus control diet for the final 2 weeks (until sacrifice at 18 weeks) LFD control for rosi: mice were fed a control low fat diet (Research Diet D12450B)
Genetic Variation Determines PPARγ Function and Anti-diabetic Drug Response In Vivo.
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View SamplesDamage to and/or loss of sensory neurons can result in debilitating neuropathies that often have a dramatic impact on quality of life. The cellular mechanisms involved in the response of neurons and glia to such pathological insults are poorly understood. Investigation has shown that peripheral glia play critical roles in both the degenerative and regenerative processes that are involved in the responses to peripheral nerve damage. The vast majority of studies have focused primarily on myelinating Schwann cells], with the result that very little is known regarding how the non-myelinating glia that ensheath axons and neuronal somas respond to nerve damage. This is a significant knowledge gap, given that over 80% of cutaneous fibers are unmyelinated, that they transduce such important modalities as itch, pain, temperature, touch and pressure, and that they are affected in many prevalent peripheral neuropathies. It is the goal of this study to shed light on the genetic programs involved in the responses of non-myelinating glia roles to nerve degeneration. We utilized RNA-seq to identify genes that were differentially expressed in the larval head during the process of sensory neuron ablation and axon degeneration in both wild-type larvae and in larvae that do not have peripheral glia (foxd3 mutants) using a selective, conditional approach. Overall, the information regarding differential gene expression in these conditions will provide a basis for further investigation into the cellular processes that underlie pathophysiological responses of neurons and glia to sensory nerve damage. Overall design: mRNA levels were determined using biological triplicate samples from five sets of samples. Three sets from wild-type: control, 2 hrs of metronidazole treatment and 5 hrs of metronidazole treatment. And two sets from foxd3 mutants: control and 5hrs of metronidazole treatment.
Transcriptome Analysis of Chemically-Induced Sensory Neuron Ablation in Zebrafish.
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View SamplesWe used the microarrays to obtain the cancerous signatures of T-cell, B-cell, erythroid and megakaryoblastic leukemias in mice.
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus.
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View SamplesCF's physiopathology is poorly explained by the mutation alone. The oxydative stress could be a major factor of this illness . Study its impact on transcriptome's CF cell line could be ameliorate our understanding of the evolution of cystic fibrosis.
Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells.
Cell line, Treatment
View SamplesThe primary objective of the study was to investigate the uncoupling protein-1 (UCP1) associated features of human epicardial adipose tissue (eAT) using next generation deep sequencing. In addition, paired mediastinal adipose tissue (mAT) and subcutaneous adipose tissue (sAT) samples colleced from patients undergoing cardic surgeries at our center were included in the study. Overall design: Paired biopsies of eAT, mAT and sAT obtained from cardiac surgery patients (n=10), with specific criteria of high- and low- expression of UCP1 in eAT, were subjected to RNA sequencing. While the primary objective was to compare high- vs. low UCP1 expression in eAT, our study design further allowed us to investigate depot- and disease specific transcriptomic shifts in these patients. Specifically, 10 patients provided 30 samples (n = 10 each for eAT, mAT and sAT) that could be compared based on depot specificity (n = 10), obesity (n = 5 lean, n = 5 obese) and coronary artery disease (CAD) (n = 6 CAD, 4 = Non-CAD).
UCP1 expression-associated gene signatures of human epicardial adipose tissue.
Disease, Disease stage, Subject
View SamplesPurpose: Single-cell RNA sequencing has revolutionized cell-type specific gene expression analysis. The goals of this study are to compare cell specific gene expression patterns between retinal cell types originating from the fovea and the periphery of human eyes. Methods: Independent libraries were prepared for foveal and peripheral samples of neural retina from three donors using the 10x Chromium system. Libraries were sequenced on a HiSeq4000. Sequenced reads were mapped to the human genome build hg19 will CellRanger(v3.0.1) and filters removed cells likely to be doublets or cells with a high proportion of mitochondrial reads. Clustering of cells with similar expression profiles was performed with Seurat (v2.3.4). Results: Independent libraries were prepared for foveal and peripheral samples of neural retina from three donors using the 10x Chromium system. Libraries were sequenced on a HiSeq4000. Sequenced reads were mapped to the human genome build hg19 will CellRanger(v3.0.1) and filters removed cells likely to be doublets or cells with a high proportion of mitochondrial reads. Clustering of cells with similar expression profiles was performed with Seurat (v2.3.4). Conclusions: Our study generates a large atlas of human retinal transcriptomes at the single cell level. We identified the majority of expected neural and supportive cell types, and describe regional differences in gene expression between the fovea and the periphery. Our results show that that single-cell RNA sequencing can be performed on human retina after cryopreservation, and that cone photoreceptors and Muller cells demonstrate region-specific patterns of gene expression. Overall design: mRNA profiles for thousands of cells from foveal and peripheral retinal isolates were generated from three human donor eyes using 10X Genomics Chromium single-cell system followed by sequencing on an Illumina HiSeq 4000.
Molecular characterization of foveal versus peripheral human retina by single-cell RNA sequencing.
Subject
View SamplesA greater understanding of the molecular pathways that underpin the unique human hematopoietic stem and progenitor cell (HSPC) self-renewal program will improve strategies to expand these critical cell types for regenerative therapies. The post-transcriptional mechanisms guiding HSPC fate during ex vivo expansion have not been closely investigated. Using shRNA-mediated knockdown, we show that the RNA-binding protein (RBP) Musashi-2 (MSI2) is required for human HSPC self-renewal. Conversely, when overexpressed, MSI2 induces multiple pro-self-renewal phenotypes, including significant ex vivo expansion of short- and long-term repopulating cells through direct attenuation of aryl hydrocarbon receptor (AHR) signaling. Using a global analysis of MSI2-RNA interactions, we determined that MSI2 post-transcriptionally downregulates canonical AHR pathway components in cord blood HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and provides evidence that manipulating such networks can provide a novel means to enhance the regenerative potential of human HSPCs expanded ex vivo. Overall design: 4 samples were used for RNA-seq (4 biological duplicate) including 2 sets of control samples (irrelvant shRNA kncok-downs)
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.
No sample metadata fields
View SamplesAlthough bodyguard (bdg), lacerata (lcr) and fiddlehead (fdh) mutations affect three unrelated genes, they trigger similar effects, i.e. ectopic organ fusion, increase of cuticle permeability. After performing cutin and wax analyses on these Arabidopsis thaliana mutants, which did not coincide with the putative enzyme functions, we hypothesised that these mutations trigger a complex response which may be visible at the transcriptional level.
Dissection of the complex phenotype in cuticular mutants of Arabidopsis reveals a role of SERRATE as a mediator.
Specimen part
View SamplesThe cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor).
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα- breast cancer.
Specimen part
View SamplesAnalysis of lineage depleted human cord blood cells sequentially transduced with retro- (BCR-ABL1) and lentiviral (Ik6) vectors and the corresponding controls. Results provide important informations on the collaboration of BCR-ABL1 and Ik6 in human hematopoietic cells.
Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts.
Specimen part
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