Lymphatic valves are specialized units regularly distributed along collecting vessels that allow unidirectional forward propulsion of the lymph, and its efficient transport from tissues to the bloodstream. Lymphatic endothelial cells that cover lymphatic valve sinuses are subjected to complex flow patterns, due to recirculation of the lymph during the collecting vessel pumping cycle. They also express high levels of FOXC2 transcription factor.
FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.
Specimen part, Treatment
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.
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View SamplesMicroglia have emerged as crucial players in the maintenance of mechanical hypersensitivity in models of chronic pain, including rheumatoid arthritis. Recent studies have suggested that there is a sexually dimorphic microglial involvement in chronic pain, but the debate is still ongoing. Here, we have used the collagen antibody-induced arthritis (CAIA) mouse model to ascertain possible differences between male and female microglia in the context of arthritis-induced pain. We have focused on the late phase of this arthritis model, when joint inflammation has resolved but mechanical hypersensitivity and microglial activation persist. We found that intrathecal administration of minocycline reversed mechanical thresholds to control levels in male, but not female mice. Moreover, we isolated resident microglia from the lumbar dorsal horns of male and female mice and observed a significantly lower number of microglial cells in females by flow cytometry analysis. Furthermore, genome-wide RNA sequencing results pointed to several transcriptional differences between male and female microglia, but no convincing differences were identified between control and CAIA groups. Taken together, these findings suggest that there are significant but subtle sex differences in microglial expression profiles independent of treatment. To what extent they help bring about the behavioural sexual dimorphism observed after minocycline administration remains to be explored. Finally, our experiments failed to identify the underlying biological correlates of the microglial activation that is present in the late phase of the CAIA model. It is likely that transcriptional changes are either subtle and highly localised and therefore difficult to identify with bulk isolation techniques or that other factors, such as changes in protein expression or epigenetic modifications are at play. Overall design: RNA-seq of male and female saline or CAIA treated mice
Exploring the transcriptome of resident spinal microglia after collagen antibody-induced arthritis.
Sex, Specimen part, Subject
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis.
Cell line
View SamplesTranscriptomic comparison of FVB mouse strain lung Cells one week upon injecting mice intraperitoneally with either saline or Urethane. Mouse lung cell were also compared at the transcriptomic level with the mouse lung adenocarcinoma cell line FULA 1, which was established in our lab
IκB Kinase α Is Required for Development and Progression of <i>KRAS</i>-Mutant Lung Adenocarcinoma.
Specimen part, Cell line, Treatment
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role for menin in the regulation of genes implicated in MEN1-like tumors.
Specimen part
View SamplesInactivating mutations in the MEN1 gene predisposing to the multiple endocrine neoplasia type 1 (MEN1) syndrome can also cause sporadic pancreatic endocrine tumors. MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone methyltransferase complexes that trimethylate histone H3 at lysine 4 (H3K4me3). The importance of menin-dependent H3K4me3 in normal and transformed pancreatic endocrine cells is unclear. To study the role of menin-dependent H3K4me3, we performed in vitro differentiation of wild-type as well as menin-null mouse embryonic stem cells (mESCs) into pancreatic islet-like endocrine cells (PILECs). Gene expression analysis and genome-wide H3K4me3 ChIP-Seq profiling in wild-type and menin-null mESCs and PILECs revealed menin-dependent H3K4me3 at the imprinted Dlk1-Meg3 locus in mESCs, and all four Hox loci in differentiated PILECs. Specific and significant loss of H3K4me3 and gene expression was observed for genes within the imprinted Dlk1-Meg3 locus in menin-null mESCs and the Hox loci in menin-null PILECs. Given that the reduced expression of genes within the DLK1-MEG3 locus and the HOX loci is associated with MEN1-like sporadic tumors, our data suggests a possible role for menin-dependent H3K4me3 at these genes in the initiation and progression of sporadic pancreatic endocrine tumors. Furthermore, our investigation also demonstrates that menin-null mESCs can be differentiated in vitro into islet-like endocrine cells, underscoring the utility of menin-null mESC-derived specialized cell types for genome-wide high-throughput studies.
Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role for menin in the regulation of genes implicated in MEN1-like tumors.
Specimen part
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
<i>NRAS</i> destines tumor cells to the lungs.
Specimen part, Cell line
View Samples