Transcriptome wide analysis of the skeletal muscle response to exercise in humans. Subjects performed one 60-min bout of moderate-intensity single-leg knee-extension exercise, and samples were obtained by biopsy of the vastus lateralis muscle before, immediately after, and at 3 hr post-exercise. Eight subjects were control (no drug), and eight received combined H1/H2-histamine receptor blockade prior to exercise. Overall design: Three time-points in each of 8 control and 8 histamine-blockade subjects. Time points are before exercise, immediately after exercise, and at 3 hrs post-exercise. Note: Alignments were re-run using an updated piece of software and the results are reported in PMID 29455450. The following supplementary files contain information on the differentially expressed genes that were identified by the new analysis of the data: GSE71972_Differential_Expression_Tables_Updated_20160830.xlsx GSE71972_Protein_Coding_Full_Counts_Updated_20160830.xlsx
A single dose of histamine-receptor antagonists before downhill running alters markers of muscle damage and delayed-onset muscle soreness.
No sample metadata fields
View SamplesGene expression analysis in control and diabetic rats. Diabetes-induced erectile dysfunction in rat model of DM. 10 weeks of streptozotocin induced diabetes. F344 Rats.
Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats.
No sample metadata fields
View SamplesBiased GPCR agonists are orthosteric ligands that possess pathway-selective efficacy, activating or inhibiting only a subset of the signaling repertoire of their cognate receptors. In vitro, D-Trp12,Tyr34-bPTH(7-34) (PTH-{beta}arr), a biased agonist for the type 1 parathyroid hormone receptor, antagonizes receptor-G protein coupling but activates arrestin-dependent signaling. In vivo, both PTH-{beta}arr and the conventional agonist PTH(1-34) stimulate anabolic bone formation. To understand how two PTH1R ligands with markedly different in vitro efficacy could elicit similar in vivo responses, we analyzed transcriptional profiles from calvarial bone of mice treated for 8 weeks with vehicle, PTH-{beta}arr or PTH(1-34). Treatment of wild type mice with PTH-{beta}arr primarily affected pathways that promote expansion of the osteoblast pool, notably cell cycle regulation, cell survival and migration. These responses were absent in beta-arrestin2 null mice, identifying them as downstream targets of beta-arrestin2-mediated signaling. In contrast, PTH(1-34) primarily affected pathways classically associated with enhanced bone formation, including collagen synthesis and matrix mineralization. PTH(1-34) actions were less dependent on beta-arrestin2, as might be expected of a ligand capable of G protein activation. These results illustrate the uniqueness of biased agonism in vivo and demonstrate that functional selectivity can be exploited to change the quality of GPCR efficacy.
β-arrestin-selective G protein-coupled receptor agonists engender unique biological efficacy in vivo.
Specimen part, Treatment
View SamplesLMP2A of Epstein-Barr virus is a receptor that mimics an activated B cell receptor, BCR. K1 and K15, related receptors of Kaposi sarcoma-associated herpes virus, KSHV, are expressed in virus-associated tumors but their functions are less obvious. We addressed this uncertainty with mutant EBVs encoding the KSHV genes K1 or K15 in lieu of LMP2A and infected primary human B cells with them. K1 and K15 encoded proteins appear to have noncomplementing redundant functions in this model but our findings suggest that both KSHV proteins can replace LMP2As key activities contributing to the survival, activation and proliferation of B cells.
K1 and K15 of Kaposi's Sarcoma-Associated Herpesvirus Are Partial Functional Homologues of Latent Membrane Protein 2A of Epstein-Barr Virus.
Specimen part, Subject
View SamplesLEM Domain proteins are key components of the nuclear lamina. Mutations in LEM-D proteins cause dystrophic diseases associated with compromised adult stem cells, yet it remains unclear how LEM-D proteins support stem cell function. Studies described here use the homologue of the LEM-D protein emerin in Drosophila, Otefin (Ote) as a model to understand LEM-D protein function in adult stem cells. Loss of Ote causes female sterility due to a complex germline stem cell (GSC) phenotype that includes both an early block in germline differentiation followed by GSC death. In vivo cell cycle analysis revealed that ote mutant GSCs display a lengthened S phase.We find that loss of the DNA Damage Response (DDR) Chk2 is able to not only rescue the lengthened S phase, but also GSC death and the block in germline differentiation. Activation of detrimental checkpoint in absence of Ote is conserved in both male and female GSCs and surprisingly occurs independent of detectable canonical DDR triggers, including transposon de-repression and DNA damage. Two defects were found to occur upstream of Chk2 activation: nuclear lamina morphological defects and altered heterochromatin organization. Together, our data identify the primary cause for a compromised adult stem cell population in the absence of a LEM-D protein.
Nuclear lamina dysfunction triggers a germline stem cell checkpoint.
Specimen part
View SamplesThis dataset was created to study M-CSF dependent in vitro differentiation of human monocytes to macrophages as a model process to demonstrate that independent component analysis (ICA) is a useful tool to support and extend knowledge-based strategies and to identify complex regulatory networks or novel regulatory candidate genes.
Analyzing M-CSF dependent monocyte/macrophage differentiation: expression modes and meta-modes derived from an independent component analysis.
Specimen part
View SamplesHaematopoietic stem cells can differentiate into all blood cell types. In this process, cells become progressively restricted to a single cell type. The order in which differentiating cells loose lineage potential, and the prospective isolation of cells with a defined potential remains a long-standing question. We performed gene expression analysis of haematopoietic cells from Gata1-EGFP reporter mice, leading to a model for hematopoiesis where the initial lineage decision consists of a seperation of erythroid/megakaryocyte/mast cell/eosinophil potential from lymphopoietic/monocyte/neutrophil potential Overall design: Find unbiased heterogeneity in the preGM hematopoietic progenitor population
Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
Specimen part, Cell line, Subject
View SamplesHaematopoietic stem cells can differentiate into all blood cell types. In this process, cells become progressively restricted to a single cell type. The order in which differentiating cells loose lineage potential, and the prospective isolation of cells with a defined potential remains a long-standing question.
Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
Specimen part
View SamplesAsthma is a heterogeneous disease requiring understandings at molecular level that characterizes subgroups of patients with specific biomarkers to faciliate the development of targeted thearpies.
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenomic enhancer profiling defines a signature of colon cancer.
Specimen part
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