Priming the cellular glycocalyx for neural development.
Ontology highlight
ABSTRACT:
SUBMITTER: Huang ML
PROVIDER: S-EPMC4198060 | biostudies-other | 2014 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing, and DNA damage. However, its in vivo function is unknown.Here we show that ppm1g expression is highly enriched in the central nervous system during mouse and zebrafish development. ppm1g(-/-) mice were embryonic lethal with incomplete penetrance after E12.5. Rostral defects, including neural tube and craniofacial defects were observed in ppm1g(-/-) embryos associated with increased cell death in the neural epithelium. In zebrafish, loss of ppm1g also led to neural defects with aberrant neural marker gene expression. Primary fibroblasts from ppm1g(-/-) embryos failed to grow without immortalization while immortalized ppm1g(-/-) fibroblasts had increased cell death upon oxidative and genotoxic stress when compared to wild type fibroblasts.Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival.
| S-EPMC4230483 | biostudies-literature
Project description:Growth factor (GF) signaling is a key determinant of stem cell fate. Interactions of GFs with their receptors are often mediated by heparan sulfate proteoglycans (HSPGs). Here, we report a cell surface engineering strategy that exploits the function of HSPGs to promote differentiation in embryonic stem cells (ESCs). We have generated synthetic neoproteoglycans (neoPGs) with affinity for the fibroblast growth factor 2 (FGF2) and introduced them into plasma membranes of ESCs deficient in HS biosynthesis. There, the neoPGs assumed the function of native HSPGs, rescued FGF2-mediated kinase activity, and promoted neural specification. This glycocalyx remodeling strategy is versatile and may be applicable to other types of differentiation.
| S-EPMC4121001 | biostudies-literature
Project description:In the mucosal epithelium, the cellular glycocalyx can project tens to hundreds of nanometers into the extracellular space, erecting a physical barrier that provides protective functions, mediates the exchange of nutrients and regulates cellular interactions. Little is understood about how the physical properties of the mucosal glycocalyx influence molecular recognition at the cellular boundary. Here, we report the synthesis of PEG-based glycopolymers with tunable glycan composition, which approximate the extended architecture of mucin glycoproteins, and tether them to the plasma membranes of red blood cells (RBC) to construct an artificial mucin brush-like glycocalyx. We evaluated the association of two lectins, ConA and SNA, with their endogenous glycan ligands on the surface of the remodelled cells. The extended glycocalyx provided protection against agglutination of RBCs by both lectins; however, the rate and magnitude of ConA binding were attenuated to a greater degree in the presence of the glycopolymer spectators compared to those measured for SNA. The different sensitivity of ConA and SNA to glycocalyx crowding likely arises from the distinct presentation of their mannoside and sialoside receptors, respectively, within the native RBC glycocalyx.
| S-EPMC6824934 | biostudies-literature
Project description:Saccharides in our diet are major sources of carbon for the formation of biomass such as proteins, lipids, nucleic acids and glycans. Among the dietary monosaccharides, glucose occupies a central role in metabolism, but human blood contains regulated levels of other monosaccharides as well. Their influence on metabolism and how they are utilized have not been explored thoroughly. Applying metabolic flux analysis on glycan synthesis can reveal the pathways that supply glycosylation precursors and provide a snapshot of the metabolic state of the cell. In this study, we traced the incorporation of six 13C uniformly labeled monosaccharides in the N-glycans, O-glycans and glycosphingolipids of both pluripotent and neural NTERA-2 cells. We gathered detailed isotopologue data for hundreds of glycoconjugates using mass spectrometry methods. The contributions of de novo synthesis and direct incorporation pathways for glucose, mannose, fructose, galactose, N-acetylglucosamine and fucose were determined based on their isotope incorporation. Co-feeding studies revealed that fructose incorporation is drastically decreased by the presence of glucose, while mannose and galactose were much less affected. Furthermore, increased sialylation slowed down the turnover of glycans, but fucosylation attenuated this effect. Our results demonstrated that exogenous monosaccharide utilization can vary markedly depending on the cell differentiation state and monosaccharide availability, and that the incorporation of carbons can also differ among different glycan structures. We contend that the analysis of metabolic isotope labeling of glycans can yield new insights about cell metabolism.
| S-EPMC7581652 | biostudies-literature
Project description:Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are responsible for hundreds of deaths in Asia and the Middle East, respectively, and are both caused by members of the genus Betacoronavirus, SARS-CoV, and MERS-CoV that were zoonotically transmitted from an animal host to humans. At present, neither vaccines nor specific treatment is available to combat coronavirus infection in humans, and novel antiviral strategies are urgently sought. The viral spike protein (S) mediates the first essential step in coronavirus infection, viral entry into target cells. For this, the S protein critically depends on priming by host cell proteases, and the responsible enzymes are potential targets for antiviral intervention. Recent studies revealed that the endosomal cysteine protease cathepsin L and the serine proteases furin and TMPRSS2 prime the S proteins of SARS-CoV and MERS-CoV and provided evidence that successive S protein cleavage at two sites is required for S protein priming. Moreover, mechanisms that control protease choice were unraveled, and insights were obtained into which enzyme promotes viral spread in the host. Here, we will provide basic information on S protein function and proteolytic priming, and we will then discuss recent progress in our understanding of the priming of the S proteins of SARS-CoV and MERS-CoV.
| S-EPMC7122371 | biostudies-literature
Project description:Female eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from ?4% of the genome. To quantitatively map the topography of XCI for defined cell types at single cell resolution, we have generated female mice that carry X-linked, Cre-activated, and nuclear-localized fluorescent reporters--GFP on one X chromosome and tdTomato on the other. Using these reporters in combination with different Cre drivers, we have defined the topographies of XCI mosaicism for multiple CNS cell types and of retinal vascular dysfunction in a model of Norrie disease. Depending on cell type, fluctuations in the XCI mosaic are observed over a wide range of spatial scales, from neighboring cells to left versus right sides of the body. These data imply a major role for XCI in generating female-specific, genetically directed, stochastic diversity in eutherian mammals on spatial scales that would be predicted to affect CNS function within and between individuals.
| S-EPMC3950970 | biostudies-literature
Project description:Invasive salmonellosis caused by Salmonella enterica involves an enteric stage of infection where the bacteria colonize mucosal epithelial cells, followed by systemic infection with intracellular replication in immune cells. The type III secretion system encoded in Salmonella Pathogenicity Island (SPI)-2 is essential for intracellular replication and the regulators governing high-level expression of SPI-2 genes within the macrophage phagosome and in inducing media thought to mimic this environment have been well characterized. However, low-level expression of SPI-2 genes is detectable in media thought to mimic the extracellular environment suggesting that additional regulatory pathways are involved in SPI-2 gene expression prior to cellular invasion. The regulators involved in this activity are not known and the extracellular transcriptional activity of the entire SPI-2 island in vivo has not been studied. We show that low-level, SsrB-independent promoter activity for the ssrA-ssrB two-component regulatory system and the ssaG structural operon encoded in SPI-2 is dependent on transcriptional input by OmpR and Fis under non-inducing conditions. Monitoring the activity of all SPI-2 promoters in real-time following oral infection of mice revealed invasion-independent transcriptional activity of the SPI2 T3SS in the lumen of the gut, which we suggest is a priming activity with functional relevance for the subsequent intracellular host-pathogen interaction.
| S-EPMC3125303 | biostudies-literature
Project description:Cross-priming is essential for generating cytotoxic T lymphocytes to viral, tumor, and tissue antigens that are expressed exclusively in parenchymal cells. In this process, the antigen-bearing parenchymal cells must somehow transfer their antigens to bone marrow-derived professional antigen-presenting cells. Although intact proteins, small peptides, or peptide-heat shock protein complexes can all be acquired and presented by antigen-presenting cells, the physiologically relevant form of antigen that is actually transferred from parenchymal cells and cross-presented in vivo is unknown and controversial. To address this issue we have investigated the ability of fibroblasts stably expressing chicken ovalbumin constructs targeted to different subcellular compartments to cross-prime cytotoxic T lymphocytes. Although these transfectants generated similar amounts of the immunogenic ovalbumin peptide, their cross-priming activity differed markedly. Instead, the cells cross-priming ability correlated with their steady-state levels of ovalbumin protein and/or the physical form/location of the protein. Moreover, in subcellular fractionation experiments, the cross-priming activity colocalized with antigenic protein. In addition, depletion of intact protein antigen from these cell fractions eliminated their cross-priming activity. In contrast, the major heat shock protein candidates for cross-presentation were separable from the cell's main sources of cross-priming antigen. Therefore, cellular proteins, rather than peptides or heat shock protein/peptide complexes, are the major source of antigen that is transferred from antigen-bearing cells and cross-presented in vivo.
| S-EPMC365740 | biostudies-other
Project description:Many studies have shown that, while reading, the brain works a sort of decomposing process of words, reducing them to its morphemes. Moreover, many studies have shown that morphological awareness, which is the ability to reflect upon the structure of words, may contribute to reading in Brazilian Portuguese. The present study investigated morphological priming in children and evaluated the correlation between morphological priming and morphological awareness scores. One hundred and forty-one children took part in this research: 35 second graders, 33 third graders, 33 fourth graders, and 40 fifth graders. They performed a lexical decision task (LDT) and morphological awareness task. Results indicate that as early as the second grade, children show some degree of morphological priming effects. In addition, children from the fifth grade presented morphological priming effects similar to those of a skilled reader. No correlations between morphological awareness scores and morphological priming effects were found.
| S-EPMC6967254 | biostudies-literature
Project description:The elicitation of cellular antiviral activities is dependent on the rapid transcriptional activation of interferon (IFN) target genes. It is not clear how the interferon target promoters, which are organized into chromatin structures in cells, rapidly respond to interferon or viral stimulation. In this report, we show that alpha IFN (IFN-alpha) treatment of HeLa cells induced hundreds of genes. The induction of the majority of these genes was inhibited when one critical subunit of the chromatin-remodeling SWI/SNF-like BAF complexes, BAF47, was knocked down via RNA interference. Inhibition of BAF47 blocked the cellular response to viral infection and impaired cellular antiviral activity by inhibiting many IFN- and virus-inducible genes. We show that the BAF complex was required to mediate both the basal-level expression and the rapid induction of the antiviral genes. Further analyses indicated that the BAF complex primed some IFN target promoters by utilizing ATP-derived energy to maintain the chromatin in a constitutively open conformation, allowing faster and more potent induction after IFN-alpha treatment. We propose that constitutive binding of the BAF complex is an important mechanism for the IFN-inducible promoters to respond rapidly to IFN and virus stimulation.
| S-EPMC400460 | biostudies-other