We used RNA sequencing to study gene expression in lymph node derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3, during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least two-fold changes. Almost three quarters of these increased during anaphylaxis Overall design: 5 Female Balb/c mice aged 4-5 weeks, were sensitized to peach using intranasally administered Pru p 3 in combination with LPS and challenged intraperitoneally as described previously . 5 Littermates, treated with intranasally administered PBS (instead of Pru p 3 and LPS), and later given an intraperitoneal challenge as per the anaphylactic mice, were used for comparison.
Transcriptional Profiling of Dendritic Cells in a Mouse Model of Food-Antigen-Induced Anaphylaxis Reveals the Upregulation of Multiple Immune-Related Pathways.
Sex, Cell line, Treatment, Subject
View SamplesDocetaxel is the standard first line therapy for hormone-refractory prostate cancer patients. Here we generated models of Docetaxel resistance in prostate cancer cells to study the molecular pathways that drive the acquisition of resistance to this therapy. We used microarrays to detail the global program of gene expression underlying the acquisition of Docetaxel resistance in prostate cancer cells.
Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.
Specimen part, Cell line
View SamplesThe combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of human iPSCs and could be used for therapeutic and regenerative medicine applications. In this study, we showed that a new first-in-class dual G9a/DNMT inhibitor CM272 compound improves the standard four-factor reprogramming efficiency of human fibroblast. The use of CM272 facilitates the generation of iPSC with only two factors, OCT4 and SOX2, allowing the removal of potentially oncogenic factors such as cMYC or KLF4. Taking a closer look at the early events occurring during cell reprogramming we demonstrated that treatment with our G9a/DNMT dual inhibitor induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to the genome and promotes mesenchymal to epithelial transition during cell reprogramming. Thus, the use of this new G9a/DNMT dual inhibitor compound may represent an interesting alternative for improving cell reprogramming.
Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.
Sex, Specimen part, Disease, Cell line
View SamplesCombined treatment with NRG-1 and DMSO led to efficient differentiation of iPS into mature ventricular-like cardiac cells, which were capable of preserving cardiac function and tissue viability when transplanted into a mouse model of myocardial infarction.
Neuregulin-1β induces mature ventricular cardiac differentiation from induced pluripotent stem cells contributing to cardiac tissue repair.
Sex
View SamplesThe transcription factor GATA2 regulates chemotherapy resistance in prostate cancer. We report a novel GATA2 transcriptional program that has implications for chemotherapy resistance disease and aggressiveness in castration resistant prostate cancer. Overall design: Examination of the transcriptional network changes induced in human Ch-CRPC cell lines by two shRNA mediated knock down of GATA2 versus random shRNA control
A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer.
No sample metadata fields
View SamplesThe purpose of this study was to determine whether postdevelopmental myostatin depletion influenced the changes in skeletal muscle gene expression profiles induced by a long-term increase in physical activity. Myostatin levels in muscles of adult male mice with floxed myostatin genes were reduced ~85% by activating Cre recombinase. Control mice with normal myostatin genes had the same Cre-activating treatment. Some of the mice were housed in ordinary cages throughout the study, limiting their physical activity. Other mice were given free access to running wheels for the final 12 weeks of the study. At the end of the study, comprehensive gene expression profiles of triceps brachii muscles were determined by RNA sequencing (RNA-Seq), with muscles from mice selected for similarity of running behavior throughout the period of wheel access. Wheel running increased expression of hundreds of mRNAs encoding proteins involved in oxidative energy metabolism, and this response was not affected by myostatin deficiency. The running-induced increase in the ratio of Myh1 mRNA (which encodes myosin heavy chain type 2x) to Myh4 mRNA (which encodes myosin heavy chain type 2b) also was not affected by myostatin depletion. At every threshold of P (computed by analysis of variance), the number of transcripts with interactions between activity level and myostatin level was fewer than the number expected by chance. These data suggest that myostatin is not required for transcriptional adaptations to moderate-intensity exercise. Overall design: 12 samples, 6 from sedentary mice and 6 from active (wheel running) mice. 3 control and 3 myostatin-deficient mice within each activity level.
Synergistic and antagonistic interplay between myostatin gene expression and physical activity levels on gene expression patterns in triceps Brachii muscles of C57/BL6 mice.
Specimen part, Subject
View SamplesThe immune system relies on the plasticity of its components to produce appropriate responses to frequent environmental challenges. Dendritic cells (DCs) are critical initiators of innate immunity and orchestrate the later and more specific adaptive immunity. The generation of diversity in transcriptional programs is central for effective immune responses. Alternative splicing is widely considered a key generator of transcriptional and proteomic complexity, but its role has been rarely addressed systematically in immune cells. Here we used splicing-sensitive arrays to assess genome-wide gene- and exon-level expression profiles in human DCs in response to a bacterial challenge. We find widespread alternative splicing events and splicing factor transcriptional signatures induced by an E. coli challenge to human DCs. Alternative splicing acts in concert with transcriptional modulation, but these two mechanisms of gene regulation affect primarily distinct functional gene groups. Alternative splicing is likely to have an important role in DC immunobiology because it affects genes known to be involved in DC development, endocytosis, antigen presentation and cell cycle arrest
Genome-wide analysis of alternative splicing during dendritic cell response to a bacterial challenge.
Specimen part, Treatment
View SamplesIdentifying the signals that regulate the survival, lineage allocation and specification of pancreas progenitors will help elucidate the embryonic origins of pancreas dysfunction and provide important cues for the efficient conversion of pluripotent stem cells into fully functional ß cells. Several transcription factors regulating the conversion of the early pancreatic progenitors into terminally differentiated cells have been identified but extracellular signals regulating pancreas development are less well understood. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata and genomics we have found that sphingosine-1-phosphate signalling through plays a key role in this process. S1p signalling stabilizes the Hippo pathway effector YAP to promote progenitor survival, acinar and endocrine specification. Endocrine cell specification relies on Gai subunits revealing an unexpected dependence of lineage specification on selected intracellular signalling components. Independently of YAP stabilization, S1p signalling attenuates Notch levels, thus regulating lineage allocation. These findings identify S1p signalling as a key pathway coordinating cell survival, lineage allocation and specification during pancreas development. Overall design: Analysis was carried out at 14.5 dpc embryonic pancreata and in 14.5 dpc embryonic pancreata that have been cultured in air to liquid interface cultures for two days (14.5 + 2). For the 14.5 dpc analysis wild type (14.5 wt) and S1pr2 null (14.5 S1pr2 null) pancreata were analyzed. For the analysis of cultured embryonic pancreata, conditions used were either standard conditions (14.5 + 2) or in the presence of 15 uM of JTE013 (14.5 + 2 + JTE) or in the presence of 15 uM of JTE013 and 50 ng/ml CTGF (14.5 + 2 + JTE + CTGF). Three biological replicates were used for each stage/condition for a total of 15 samples.
Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.
Cell line, Subject
View SamplesIn this study, genome-wide gene expression profiles of primary hepatocytes and liver sinusoidal endothelial cells (LSECs) were measured at day 12 for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA). The culture systems analyzed include the commonly used collagen sandwich and monolayers of hepatocytes, as well as 3-dimensional (3D) engineered liver models that contain hepatocytes and LSECs (3DHL) and hepatocytes, LSECs, and Kupffer cells (3DHLK). Our results highlight the up-regulation of several hepatocyte specific functions in hepatocytes and a novel interplay between Ppara signaling and bile acid biosynthesis in LSECs.
Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models.
Specimen part, Time
View SamplesThe Anopheles gambiae midgut harbors bacteria that proliferate upon a blood feed. We used microarrays to examine the midgut gene expression response at early stages (3hours) after an artifitial meal containing heat killed bacteria.
A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae.
Age, Specimen part
View Samples