Posterior embryonic axis develops from neuromesodermal progenitors which differentiate into neural tube and paraxial mesoderm
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Treatment
View SamplesStem cell-derived tissues have wide potential for modelling developmental and pathological processes as well as cell-based therapy. However, it has proven difficult to generate several key cell types in vitro, including skeletal muscle. In vertebrates, skeletal muscles derive during embryogenesis from the presomitic mesoderm (PSM). Using PSM development as a guide, we establish conditions for the differentiation of monolayer cultures of human pluripotent stem (hPSC) cells into PSM-like cells without the introduction of transgenes or cell sorting. We differentiated human PSCs in serum-free medium supplemented with Chir99021 only (C medium) or with also the Bmp inhibitor LDN193189 (CL medium). In vivo, the PSM cells are first expressing MSGN1 (posterior PSM marker) and then mature to express Pax3 (anterior PSM marker). After 4-5 days of differentiation of hPSCs, MSGN1-positive cells were FACS-sorted and their transcriptome analyzed.
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Treatment
View SamplesThe purpose of the experiment was to generate a time course of gene expression following irradiation. The goal was then to model this data to extract hidden variables - chiefly, the activity profiles of the p53 transcription factor. Using this information the aim was to predict which transcripts changed by IR were targets of p53. Cells in log phase (1 x 106 ml-1) were ?-irradiated with 5 Gy at room temperature (RT) at a dose rate of 2.45 Gy per minute with a 137Cs ?-irradiator. Cells were harvested at 0, 2, 4, 6, 8, 10 and 12 hours, and RNA and protein were extracted (Trizol, Invitrogen). Affymetrix U133A arrays were hybridized as standard (www.affymetrix.co.uk). Array quality was determined using R and GCOS .rpt file values. The time course was replicated three times from independent cell preparations.
Ranked prediction of p53 targets using hidden variable dynamic modeling.
Specimen part, Disease, Cell line, Time
View SamplesBackground
Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes.
Sex, Disease
View SamplesChildren with oligoarticular JIA (arthritis in 4 or fewer joints) can either continue to have this mild form of arthritis (persistent oligoarticular JIA) or extend to a more sever form involving more than 4 joints (extended oligoarticular JIA)
Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression.
Specimen part
View SamplesAtaxin 1 (Atxn1) is a protein of unknown function associated with cerebellar neurodegeneration in spinocerebellar ataxia type 1 (SCA1). SCA1 is caused by an expanded polyglutamine within Atxn1 by gain-of-function mechanisms. Lack of Atxn1 in mice triggers motor deficits in the absence of neurodegeneration or apparent neuropathological abnormalities.We extracted RNA from cerebellum of 5 Atxn1-null mice and 5 WT. Cerebellar gene expression profiles at 15 weeks of age were generated usSCA1 ing Affymetrix MOE430A arrays. Identifying the molecular pathways regulated by Atxn1 can provide insights into the early molecular mechanisms underlying neuronal dysfunction.
Down-regulation of the dopamine receptor D2 in mice lacking ataxin 1.
Age, Specimen part
View SamplesSkeletal muscle adapts to exercise training of various modes, intensities and durations with a programmed gene expression response. This study dissects the independent and combined effects of exercise mode, intensity and duration to identify which exercise has the most positive effects on skeletal muscle health. Full details on exercise groups can be found in: Kraus et al Med Sci Sports Exerc. 2001 Oct;33(10):1774-84 and Bateman et al Am J Cardiol. 2011 Sep 15;108(6):838-44.
Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.
Sex, Age, Specimen part, Race, Subject
View SamplesAcute liver injury is a critical life-threatening event. Common causes are infections, intoxication, and ischemic conditions. The cytokine Interleukin 22 (IL-22) has been implicated in this process. However, the role of IL-22 during acute liver damage is controversial, since both protective and pathogenic properties have been reported. IL-22 binding protein (IL-22BP, IL-22Ra2), a soluble endogenous inhibitor of IL-22, is able to regulate IL-22 activity, and thus might explain some of the controversial findings. Since the role of IL-22BP in liver injury is unknown, we used Il22bp deficient mice and mouse models for acute liver damage to address this point. We found that Il22bp deficient mice were more susceptible to ischemia- and acetaminophen- induced liver damage. Deficiency of Il22bp caused increased hepatic damage and delayed liver regeneration. Using an unbiased approach, we found that IL-22, if uncontrolled in Il22bp deficient mice, induced Cxcl10 expression by hepatocytes, thereby recruiting inflammatory CD11b+Ly6C+ monocytes into the liver upon liver damage. Accordingly, neutralization of Cxcl10 reversed the increased disease susceptibility of Il22bp deficient mice. In conclusion, our data suggest dual functions of IL-22 in acute liver damage, and highlight the need to control IL-22 activity via IL-22BP. Overall design: RNA sequencing of RNA isolated from liver tissue from mice that underwent liver reperfusion treatment (IR) or sham surgery, in triplicate for three genotypes (Wt, Il22-/- and Il22bp-/-).
A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury.
Specimen part, Treatment, Subject
View SamplesGene expression on peripheral blood mononuclear cells (PBMC) from SPARKS CHARMS juvenile idiopathic arthritis (JIA) cohort pre and post methotrexate therapy. This is the first study to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyze genetic variation in differentially expressed genes. We have identified a gene, which may contribute to genetic variability in MTX response in JIA.
Generation of novel pharmacogenomic candidates in response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype.
Specimen part, Treatment, Subject
View SamplesThe transcriptional effects of urocortin I, urocortin II and tempol were compared to saline treatment in a rat model of in vivo coronary artery occlusion model of ischaemia/reperfusion injury of 25 min ischaemia and 2 hr reperfusion. <br></br>The treatment groups were as follows (i) sham operation or LAD occlusion with infusion of (ii) saline, (iii) 15 ?g/kg Ucn I, (iv) 15 ?g/kg Ucn II and (v) 100 mg/kg tempo infused just prior to reperfusionl.<br></br>Following 2 hr reperfusion the left ventricle was removed, snap frozen, followed by RNA extraction.
New targets of urocortin-mediated cardioprotection.
Sex, Age, Specimen part, Disease, Disease stage, Subject, Compound, Time
View Samples