Presentation of immunoregulatory sialoglycans on T cells is divergent between mice and humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE276900 | GEO | 2025/05/26
REPOSITORIES: GEO
Similar Datasets
Project description:Glycosylation is the most common post-translational modification of proteins, yet genes relevant to the synthesis of glycan structure and function are incompletely represented and poorly annotated on the commercially available arrays. To fill the need for expression analysis of such genes we employed the Affymetrix technology to develop a focused and highly annotated glycogene chip representing human and murine glycogenes, including glycosyltranferases, nucleotide sugar transporters, glycosidases, proteoglycans and glycan-binding proteins. In this report the array has been used to generate glycogene expression profiles of nine murine tissues. Global analysis with a hierarchical clustering algorithm, reveals that expression profiles in immune tissues (thymus, spleen, lymph node and bone marrow) are more closely related, relative to those of non-immune tissues (kidney, liver, brain and testes). Of the biosynthetic enzymes, those responsible for synthesis of the core regions of N-and O-linked oligosaccharides are ubiquitously expressed, while glycosyltransferase that elaborate terminal structures are expressed in a highly tissue-specific manner, accounting for tissue and ultimately cell type-specific glycosylation. Comparison of gene expression profiles with MALDI-TOF profiling of N-linked oligosaccharides suggested that the alpha-1-3 fucosyltransferase IX, Fut9, is the enzyme responsible for terminal fucosylation in kidney and brain, a finding validated by analysis of Fut9 knockout mice. Two families of glycan-binding proteins, C-type lectins and siglecs, are predominately expressed in the immune tissues, consistent with their emerging functions in both innate and acquired immunity. The glycogene chip reported in this study is available to the scientific community through the Consortium for Functional Glycomics (http://www.functionalglycomics.org). Keywords: Glycogenes, Glycomics, Glycosyltransferase, Lectin, Glycosylation, Glycome, Microarray, Kidney, Fut9
2005-06-20 | GSE2781 | GEO
Project description:Siglecs are a family of receptor-type glycan recognition proteins (lectins) involved in self - nonself discrimination by the immune system. Identification of Siglec ligand(s) is necessary to understand how Siglec-ligand interaction translates to biological outcomes, but is challenging because the interaction is weak. To facilitate identification of Siglec ligands, we adopted proximity labeling method based on tyramide radicalization principle.
2017-09-29 | PXD006359 | Pride
Project description:Germinal centres (GC) are specialized sites where B cells expand and diversify their antibody genes through somatic hypermutation. GC B-cells are routinely identified through distinct changes on their surface carbohydrates, known as glycans. One striking modification relates to the monosaccharide sialic acid. In mice, this change is mediated through downregulation of an enzyme called CMAH, which results in a GC-specific loss of preferred ligand for CD22, a member of the sialic acid-binding immunoglobulin-type lectins (Siglecs) and an inhibitory co-receptor of the B-cell antigen receptor (BCR). Here, we identified that glycan remodeling, mediated by downregulation of CMAH, is crucial for the GC B-cell response, and production of memory B-cells, plasma cells, and high affinity antibodies. We also demonstrated that the function of these altered glycans is dependent on CD22, highlighting that coordinated loss of preferred ligands acts to modulates the CD22 activity in the GC B-cells. Overall, our study reveals that intrinsic glycan remodeling functions to optimize the B-cell responses in the GC by controlling CD22.
2022-02-09 | GSE196206 | GEO
Project description:The UT-A1 urea transporter is crucial to the kidney’s ability to generate concentrated urine. Native UT-A1 from kidney inner medulla (IM) is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, UT-A1 protein abundance, particularly the 117 kD isoform, is significantly increased corresponding to an increased urea permeability in perfused IM collecting ducts, which plays an important role in preventing the osmotic diuresis caused by glucosuria. In this study, using sugar-specific binding lectins, we found that the carbohydrate structure of UT-A1 is also changed under diabetic conditions with increased amounts of sialic acid, fucose, and increased glycan branching. These changes were accompanied by altered UT-A1 association with the galectin proteins, α-galactoside glycan binding proteins. To explore the molecular basis of the alterations of glycan structures, the highly sensitive next generation sequencing (NGS) technology, Illumina RNA-seq, was employed to analyze genes involved in the process of UT-A1 glycosylation using streptozotocin (STZ) - induced diabetic rat kidney as the tissue source. Differential expression analysis combining quantitative PCR revealed that a number of important glycosylation related genes were changed under diabetic conditions. These genes include the glycosyltransferase genes Mgat4a, the sialylation enzymes St3gal1 and St3gal4and glycan binding protein galectin-3, -5, -8 and -9. In contrast, although highly expressed in kidney IM, the glycosyltransferase genes Mgat1, Mgat2, and fucosyltransferase Fut8, did not show any changes. We conclude that the alteration of these glycosylation related genes may contribute to changing the UT-A1 glycan structure, and therefore modulate kidney urea transport activity under diabetic conditions.
2017-02-09 | GSE69548 | GEO
Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS227 Abstract:"Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation."
2018-08-07 | MSV000082793 | GNPS
Project description:The majority of cell surface and secreted proteins are modified by glycans and this glycosylation process plays an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signalling. Glycosylation plays an important role in myogenesis and the development of muscle tissue but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during in vitro myogenesis. We observed wide-spread changes in the abundance of several receptors and important enzymes regulating glycosylation. Quantification of released N-linked glycans via glycomic analysis confirmed remodeling of the glycome with a switch in sialic acid linkages, and changes in di-galactosylation and paucimannosylation. Quantitative glycoproteomic analysis with stable isotope labelling, enrichment of glycopeptides and analysis via multiple fragmentation approaches identified precise glycoproteins containing these regulated glycans including integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins including the up-regulation of Galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early defect in the myogenic program. We also observed similar changes in N-glycosylation and the up-regulation of LGALS1 during postnatal skeletal muscle development in mice. Finally, treatment of new-born mice with recombinant adeno-associated viruses to express LGALS1 in the musculature resulted in enhanced muscle mass. Our data will be a valuable resource to further understand the role of glycosylation and lectins on myogenesis and may aid in the development of intervention strategies aimed at promoting healthy muscle.
2021-01-29 | PXD021006 | Pride
Project description:The majority of cell surface and secreted proteins are modified by glycans and this glycosylation process plays an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signalling. Glycosylation plays an important role in myogenesis and the development of muscle tissue but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during in vitro myogenesis. We observed wide-spread changes in the abundance of several receptors and important enzymes regulating glycosylation. Quantification of released N-linked glycans via glycomic analysis confirmed remodeling of the glycome with a switch in sialic acid linkages, and changes in di-galactosylation and paucimannosylation. Quantitative glycoproteomic analysis with stable isotope labelling, enrichment of glycopeptides and analysis via multiple fragmentation approaches identified precise glycoproteins containing these regulated glycans including integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins including the up-regulation of Galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early defect in the myogenic program. We also observed similar changes in N-glycosylation and the up-regulation of LGALS1 during postnatal skeletal muscle development in mice. Finally, treatment of new-born mice with recombinant adeno-associated viruses to express LGALS1 in the musculature resulted in enhanced muscle mass. Our data will be a valuable resource to further understand the role of glycosylation and lectins on myogenesis and may aid in the development of intervention strategies aimed at promoting healthy muscle.
2022-02-15 | PXD019372 | Pride
Project description:Analysis of mucin-type O-glycan regulation of gene expression in murine intestinal epithelial cells isolated from a mouse. The hypothesis tested in the current study was that loss of Cosmc (by Cre/Lox: Vil-Cre+ X Cosmcflox/+), which is required for core 1-based O-glycan extension, influences gene expression. Transcripts from colorectum and from small intestine were compared to also evaluate whether O-glycans control different genes in different regions of the gut. We had particular interest in identifying transcripts or pathways important in regulating the microbiota or influencing intestinal inflammation. Results provide important information on how cell surface glycosylation controls gene transcription in in vivo.
2016-12-18 | GSE84416 | GEO
Project description:Aberrant glycosylation is a characteristic of tumor cells. The expression of certain glycan structures has been associated with poor prognosis. In cervical carcinoma has been reported changes in the gene expression level of some glycogenes that has been associated with lymph invasion. Human papilloma virus (HPV) infection is one of the most important factors to develop cervical cancer. HPV oncoproteins E6 and E7 have been implicated in cervical carcinogenesis. The role of these oncoproteins in glycosylation changes has not been reported. To know the effect of these oncoproteins on glycogene expression we realized a partial silencing of oncogenes E6 and E7 in HeLa cells, we made a microarray expression assay and we identified glycogenes that modified its expression. The analysis showed alteration in some glycosylation pathways, like glycosphingolipid, O-glycan mucin-type, and O-glycan non mucin-type glycosylation. Our results suggest that E6 and E7 oncoproteins could modified glycosylation of structures implicated in proliferation, adhesion, and apoptosis.
2016-12-07 | GSE90930 | GEO
Project description:Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation.
2017-02-03 | MTBLS227 | MetaboLights