Male C57BL/6 mice were treated with ENU to generate single base substitutions, the variant genome sequences were breed to homozygosity in inbreeding pedigrees, and screened for antinuclear autoantibodies (ANA). The sanroque pedigree contained multiple progeny with ANA of mixed homogeneous nuclear and cytoplasmic immunofluorescence pattern by 12 weeks of age, due to an autosomal recessive gene variant. Comparison of the gene expression profile of CD4 cells from Sanroque to wild type was performed.
A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity.
No sample metadata fields
View SamplesDevelopment of T-cells provides a unique opportunity to study cell-fate determination due to the accessability and the well defined stages of development. In order to understand the genetic programs underlying fetal and adult Tcell fate specification we subjected highly purified fetal and adult T-cell progenitor populations to a genomewide transcriptional analysis. The aim was to identify molecular elements that govern T-cell fate specification as a whole but ultimately to isolate elements that were specific for a given population in a specific developmental window.
Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages.
Sex
View SamplesVisceral leishmaniasis (VL), caused by Leishmania spp protozoan parasites, can provoke overwhelming and protracted epidemics, with high casefatality rates. Despite extensive efforts towards the development of an effective prophylactic vaccine, no promising vaccine is available yet for humans. Multi-epitope peptide based vaccine development is manifesting as the new era of vaccination strategies against VL. Aim of the study was the design of chimeric peptides from immunogenic L. infantum proteins for encapsulation in PLGA nanoparticles (NPs) alone or in combination with MPLA adjuvant, or in PLGA NPs surface modified with an octapeptide mimicking TNF-alpha for DCs targeting, in order to construct a peptide-based nanovaccine. The in vitro evaluation of the above nanoformulations was performed in DCs isolated from HLA-A2.1 transgenic mice. Characterization of DCs transcriptional responses to these vaccine candidates via microarrays could improve our understanding of their mechanisms of action on DCs' functional differentiation and the type of adaptive immunity subsequently induced.
A Poly(Lactic-<i>co</i>-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different <i>Leishmania infantum</i> Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8<sup>+</sup> T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.
Specimen part
View SamplesVisceral leishmaniasis (VL) caused by Leishmania donovani and L. infantum is a potentially fatal disease. To date there are no registered vaccines for disease prevention despite the fact that several vaccines are in preclinical development. Thus, new strategies are needed to improve vaccine efficacy based on a better understanding of the mechanisms mediating protective immunity and mechanisms of host immune responses subversion by immunopathogenic components of Leishmania. In the present study, determination of the immune mechanisms related to infection or protective immune responses against VL using an experimental nanovaccine as a vaccine model was conducted through microarray analysis.
Transcriptome Analysis Identifies Immune Markers Related to Visceral Leishmaniasis Establishment in the Experimental Model of BALB/c Mice.
No sample metadata fields
View SamplesGroucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. A pro-oncogenic potential for GRG5 is revealed by the malignant behavior of teratomas generated from ESCs that overexpress it. Furthermore, transcriptomic analysis and cell differentiation approaches underline GRG5 as a multifaceted signaling regulator that represses mesendodermal-related genes. When ES cells exit pluripotency, GRG5 promotes neuroectodermal specification via Wnt and BMP signaling pathways suppression. Moreover, GRG5 promotes the neuronal reprogramming of fibroblasts and maintains the self-renewal of Neural Stem Cell (NSC) by sustaining the activity of Notch and Jak/Stat3 pathways. In summary, our results demonstrate that GRG5 has pleiotropic roles in stem cell biology functioning as a stemness factor and a neural fate specifier. Overall design: Gene expression profiling of control and Grg5 knockdown (KD) embryonic stem cells with RNA-seq, in dublicate, using Ion Torrent Proton.
Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions.
Cell line, Subject
View SamplesThe aim of this work was to produce a reproducible molecular signature of human muscle responses to resistance training and examine how such a profile relates to new and established exercise adaptation gene networks.
Molecular networks of human muscle adaptation to exercise and age.
Age, Specimen part, Subject, Time
View SamplesThe overall objective of the heritage project is to study the role of the genotype in cardiovascular,metabolic and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in several cardiovascular disease and diabetes risk factors.
Molecular networks of human muscle adaptation to exercise and age.
Age, Specimen part, Subject, Time
View SamplesWe generated a murine genetic model of beta-catenin deficiency targeted to the ureteric bud cell lineage to study the role of beta-catenin mediated Wnt signaling during ureteric morphogenesis.
Canonical WNT/beta-catenin signaling is required for ureteric branching.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Atrial identity is determined by a COUP-TFII regulatory network.
Age, Specimen part
View SamplesAtria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules.
Atrial identity is determined by a COUP-TFII regulatory network.
Age, Specimen part
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