Project description:This experiment aimed at characterising the modulatory role of murine induced Neural Stem Cells (iNSCs) and Neural Stem Cells (NSCs) on macrophages (MPs) exposed to LPS in vitro. Naïve MPs were polarized into an M1-like phenotype with LPS, and then co-cultured with 1:1 ratios of iNSCs in a trans-well system that avoids cell-to-cell contacts. Naïve MPs, LPS-stimulated MPs and LPS-stimulated MPs co-cultured with NSCs were used as controls.
Project description:We conclude that Nf1Myf5 MPs are driven towards quiescence and show metabolic reprogramming with severely inhibited glycolytic metabolism that, in turn impinges on H4K16ac decoration and expression of myogenic differentiation-related genes. ChIP-Seq analysis of freshly isolated p7 MPs showed apparently unaltered H3K4me3 levels between controls and Nf1Myf5 MPs, while H3K27me3 levels were globally reduced in Nf1Myf5 MPs. A reduction of H3K27me3 decoration was observed at genes associated with quiescence as Pax7, or with cell cycle repression as Cdkn2a. The assumption of a quiescent state in Nf1Myf5 MPs is concomitant to decreased repressive H3K27me3 modification at quiescence-associated genes.
Project description:Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme beta-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation. In this study we performed microarray analysis of ascending aortas from normal and MPS VII mice, trying to find out possible genes responsible for the phenotype observed. In addition, during our breeding strategy, we noticed that some MPS VII mice had less dilated aortas, and we proposed that an yet-unidentified gene could be responsible for the difference observed. We therefore included in the analysis two MPS VII mice with aortas that were not dilated. Total RNA extracted from ascending aortas from 3 Normal mice, 3 MPS VII mice with dilated aortas and 2 MPS VII mice with aortas that were not dilated.
Project description:We used microarray to detect pathway differences in the various brain regions in a monogenic in mucopolysaccharidosis type VII ( MPS VII ), a mouse model of a lysosomal storage disease A number of changes revealed unexpected system and process alterations, such as upregulation of the immune system with few inflammatory changes (a significant difference from the closely related MPS IIIb model), down-regulation of major oligodendrocyte genes even though white matter changes are not a feature histopathologically, and a plethora of developmental gene changes. 94 samples, no replicates, made up of half normals and half MPS mutant mice for the MPS VII mutation backcrossed on a C3h-heouj background
Project description:Plastic is widespread in our lives, releasing various Microplastics (MPs) with toxicity. In recent years, the potential threat of MPs on reproductive system arouses public concern. Numerous reports have focused on its damage to spermatogenesis. Nevertheless, the toxicity of MPs on female reproduction is unclear. Here, we explored this question using bovine oocyte. We found that MPs disrupts spindle organization, chromosomes alignment and actin assembly, leading to failed maturation of bovine oocytes. Meanwhile, cortical granule secretion is obstructed, suggesting the failure of cytoplasmic maturation. Therefore, embryonic development is impacted. In transcriptome results, MPs induces the expression change of Mitochondrial-related genes, reflecting the damage of MPs are mediated by mitochondrial functions. MPs indeed causes oxidative stress, DNA damage and apoptosis. Taurine is capable for stabilizing cellular antioxidant level. We surprisingly find that Taurine suppresses mitochondrial dysfunction, reversing the failure of oocyte maturation and embryo development after MPs exposure. Collectively, we reveal the reproduction toxicity of MPs on bovine oocytes, and demonstrates the restorative effect of Taurine against MPs.
Project description:Comparisons of canine arterial gene expression between control and untreated MPS animals were conducted with a canine-specific microarray covering 43,803 probes (Agilent G2519F 4x44k, Santa Clara, CA), for a total of four comparison groups: MPS ascending aorta vs. control ascending aorta, MPS descending aorta vs. control descending aorta, MPS carotid artery vs. control carotid artery, and finally pooled MPS artery (ascending aorta, descending aorta, carotid artery) vs. pooled control artery. Each comparison used four pairs of MPS vs corresponding age- and gender- matched animals to produce four biologic replicates.
Project description:Background : In mucopolysaccharidosis type III (MPS III, also known as Sanfilippo syndrome), a pediatric neurodegenerative disorder, accumulation of abnormal glycosaminoglycans (GAGs) induces severe neuroinflammation by triggering the microglial pro-inflammatory cytokines production via a TLR4-dependent pathway. But the extent of the microglia contribution to the MPS III neuropathology remains unclear. Extracellular vesicles (EVs) mediate intercellular communication and are known to participate in the pathogenesis of adult neurodegenerative diseases. However, characterization of the molecular profiles of EVs released by MPS III microglia and their effects on neuronal functions have not been described. Methods : Here, we isolated EVs secreted by the microglial BV-2 cells after treatment with GAGs purified from urines of Sanfilippo patients (MPS-GAGs EVs) or from age-matched healthy subjects (WT-GAGs EVs) to explore the EVs’ proteins and small RNA profiles using LC–MS/MS and RNA sequencing. We next performed a functional assay by immunofluorescence following WT-GAGs- or MPS-GAGs-EVs uptake by WT primary cortical neurons and analyzed their extensions metrics after staining of βIII-tubulin and MAP2 by confocal microscopy. Results : Functional enrichment analysis for both proteomics and RNA sequencing data from MPS-GAGs-EVs revealed a specific content involved in neuroinflammation and neurodevelopment pathways. Treatment of cortical neurons with MPS-GAGs-EVs induced a disease-associated phenotype demonstrated by a lower total neurite surface area, an impaired somatodendritic compartment, and a higher number of immature dendritic spines. Conclusions : This study shows, for the first time, that GAGs from patients with Sanfilippo syndrome can induce microglial secretion of EVs that deliver a specific molecular message to recipient naive neurons, while promoting the neuroinflammation, and depriving neurons of neurodevelopmental factors. This work provides a framework for further studies of biomarkers to evaluate efficiency of emerging therapies.
Project description:Microplastics (MPs) as widespread contamination pose high risk for aquatic organisms.Intestinal microbiotahas have high interaction with immune system of host body. In this study, intestinal microbiota of zebrafish after Polystyrene (PS-MPs) exposure were characterized by 16S rDNA amplicon sequencing. We found that 100nm and 200μm PS-MPs exposure significantly increased diversity of intestinal microbiota and all the three sizes of PS-MPs increased abundance of pathogenic bacteria.