Major- and minor-group rhinoviruses enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Even though major- and minor-group rhinoviruses are nearly genetically identical, these viruses do not replicate with equal success in monocyte-lineage cell lines. In human primary macrophages, differential mitochondrial activity and signaling pathway activation was observed between major- and minor-group rhinovirus upon initial HRV binding, indicating discordant receptor-dependent response to these rhinovirus types. As well, variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor- group HRV treatments. The difference between major- and minor- group HRV activation of signaling pathways was confirmed through RNA-sequencing and observation of differential production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages. These results suggest that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in part by monocytic-lineage cells in the human airway upon exposure to rhinovirus. Overall design: RNA sequencing of monocyte-derived macrophages after mock infection or infection by HRV16 or HRV1A
Major and minor group rhinoviruses elicit differential signaling and cytokine responses as a function of receptor-mediated signal transduction.
No sample metadata fields
View SamplesT cell lymphoma
PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis.
Sex, Specimen part, Cell line
View Samplesused to identify differences between tissues from patients undergoing surgery for BPH with unresolved symptoms compared to incidental BPH from patients with prostate cancer
Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.
Specimen part
View SamplesWhile skeletal myogenesis is tightly coordinated by myogenic regulatory factors including MyoD and myogenin, chromatin modifications have emerged as vital mechanisms of myogenic regulation. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor, promotes the specification and differentiation of skeletal muscle lineage. Here, we examine a genome-wide impact of rexinoids on myogenic differentiation through integral RNA-seq and ChIP-seq analyses. We found that bexarotene promotes myoblast differentiation through the coordination of exit from the cell cycle and the activation of muscle-related genes. We uncovered a new mechanism of rexinoid action which is mediated by the nuclear receptor and largely reconciled through a direct regulation of MyoD gene expression. In addition, we determined a rexinoid-responsive residue-specific histone acetylation at a distinct chromatin state associated to MyoD and myogenin. Thus, we provide novel molecular insights into the interplay between retinoid X receptor signaling and chromatin states pertinent to myogenic programs in early myoblast differentiation. Overall design: We have profiled the global effect of bexarotene, a selective agonist of retinoid X receptor on myoblast gene expression by RNA-seq analysis using RNA isolated from C2C12 myoblasts following 12 or 24 hours of differentiation in the presence and absence of 50 nM bexarotene, with 2 biological replicates. Proliferating myoblasts were used as controls.
Insights into interplay between rexinoid signaling and myogenic regulatory factor-associated chromatin state in myogenic differentiation.
Cell line, Subject
View SamplesCTSK-mGFP positive cells from Day 6 old mouse femurs were sorted as single cells into 384 well plates pre-loaded with unique barcoded RT-primers. After sorting, cells were snap frozen on dry ice before being submitted to the New York Genome Center (NYGC) for cDNA synthesis and library preparation. The FACS profile for all the sored cells were collected to co-relate with gene expression. Overall design: Mouse femur was obtained from mice within the same litter. Femur samples was subjected to collagenase digestion, and single cell suspension was obtained. The samples were stained for FACS antibodies and single cell sorting was performed into two individual 384 well plates. The experiment has two replicates from two independant animals. The samples were always kept discrete.
Discovery of a periosteal stem cell mediating intramembranous bone formation.
Specimen part, Cell line, Subject
View SamplesAZD1208 is a novel PIM kinase inhibitor that we have shown inhibits tumorigenesis in tissue recombination models, Myc-CaP allograft models, and human prostate cancer xenografts. We sought to determine the intracellular pathways that are responsible for the anti-tumor effect. To this end we used the tissue recombination protocol to implant MYCCaP cells into castrated mice. MYCCaP cells are an androgen-dependent mouse cell line that overexpresses the oncogene MYC. The mice used for implantation were castrated, so any tumors that result from the grafting procedure are androgen-independent. The grafted mice were divided into a control population receiving vehicle, and a test population receiving AZD1208. The tumors were harvested and in vitro cell lines were made. The new cell lines have been perpetuated in androgen-depleted media.
PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer.
Cell line
View SamplesGS-5759 is a bifunctional ligand composed of a quinolinone-containing pharmacophore found in several 2-adrenoceptor agonists linked covalently to a phosphodiesterase 4 inhibitor (PDE4) related to GSK 256066 by a pent-1-yn-1-ylbenzene spacer. The object of the study was to detemine if gene expression changes induced by GS-5759 were replicated by a 2-adrenoceptor agonist (indacaterol; Ind) and a PDE4 inhibitor (GSK 256066; GSK) in combination.
GS-5759, a Bifunctional β2-Adrenoceptor Agonist and Phosphodiesterase 4 Inhibitor for Chronic Obstructive Pulmonary Disease with a Unique Mode of Action: Effects on Gene Expression in Human Airway Epithelial Cells.
Cell line, Treatment
View SamplesMononuclear phagocytes are a diverse cell family that occupy all tissues and assume numerous functions to support tissue and systemic homeostasis. Our ability to investigate the roles of individual subsets is limited by an absence of approaches to ablate gene function within specific sub-populations. Using Nr4a1-dependent Ly6Clow monocytes as a representative cell type we show that enhancer deletion addresses these limitations. Combining ChIP-Seq and molecular approaches we identify a single, conserved, sub-domain within the Nr4a1 enhancer that is essential for Ly6Clow monocyte development. Mice lacking this enhancer lack Ly6Clow monocytes but retain Nr4a1 gene expression in macrophages during steady state and in response to LPS. Nr4a1 is a key negative regulator of inflammatory gene expression and decoupling these processes allows Ly6Clow monocytes to be studied without confounding influences. Enhancer targeting possesses greater specificity than cre recombinase-mediated gene deletion, providing a route to generate loss-of-function models in closely related cell types. Overall design: Paired End mRNA sequencing of FACS purified primary murine MDP, cMoP, Ly6Chi and Ly6Clow monocytes from the bone marrow and Ly6Chi and Ly6Clow monocytes from the peripheral blood
Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6C<sup>low</sup> Monocytes while Preserving Macrophage Gene Function.
Specimen part, Cell line, Subject
View SamplesThe goal of this study is to understand the alterations in transcriptome induced by histone H3K36M mutations Overall design: Transcritome profiling of 3 cell lines cultured in vitro and 6 murine tumors
Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Specimen part, Cell line, Treatment
View Samples