Glycosphingolipids of human embryonic stem cells

Breimer, Michael E.; Säljö, Karin; Barone, Angela; Teneberg, Susann

doi:10.1007/s10719-016-9706-y

Cited by 23 publications

(19 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gangliosides with multiple sialylation such as GT1, GD3, GD2 and GD1 also increased in neural cells. The shift in the neural glycomic profile toward a greater abundance and density of sialic acids is in good agreement with published literature, albeit on other cell lines ( Park et al 2015 ; Breimer et al 2017 ).…”

Section: Resultssupporting

confidence: 91%

“…Differentiation can also alter the glycomic landscape on the cell surface, reflecting the evolution in the functions of the cell ( Hakomori 1981 ; Lau et al 2007 ). Pluripotency is linked to the increased expression of N -glycan high mannose structures ( Hasehira et al 2012 ) and globo-type glycosphingolipid (GSL) structures, particularly stage-specific embryonic antigens (SSEA), which are regarded as markers for cell pluripotency ( Breimer et al 2017 ). When differentiated into neural progenitors, GSL expression is shifted from globo- and lacto-type structures to sialylated gangliosides ( Liang et al 2011 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic flux analysis of the neural cell glycocalyx reveals differential utilization of monosaccharides

Wong

Barboza

et al. 2020

Glycobiology

View full text Add to dashboard Cite

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 has 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.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Metabolic flux analysis of the neural cell glycocalyx reveals differential utilization of monosaccharides

Wong

Barboza

et al. 2020

Glycobiology

View full text Add to dashboard Cite

show abstract

“…Both the H-type 1 and Globo H antigens are present on pluripotent cells and can be used as glyco-markers. The Globo H glycosphingolipid is also highly expressed on malignant tissues, particularly in breast and small cell lung cancers [24,25]. Globo H presents the H-type 3 antigen (Fucα1-2Galβ1-3GalNAc) which only differs from H-type 1 antigen (Fucα1-2Galβ 1-3GlcNAc) by the epimerization of GlcNAc at C4 position.…”

Section: Discussionmentioning

confidence: 99%

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

2020

View full text Add to dashboard Cite

Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.

show abstract

“…ectoderm, mesoderm and endoderm) (Liang et al, 2010(Liang et al, , 2011Russo et al, 2018) (Table S1). Pluripotent stem cells express GSLs of the globo and lacto series (Breimer et al, 2017;Liang et al, 2010Liang et al, , 2011Russo et al, 2018), including Gb3, Gb4, Gb5 (SSEA-3), α1-2 fucosylated-Gb5 (Globo H), sialyl-Gb5 (SSEA-4) and disialyl-Gb5, globo-A, Lc3, Lc4, SSEA-1 and fucosyl-Lc4 (Breimer et al, 2017) (Fig. 3).…”

Section: Gsl Reprograming In Development Cell Differentiation and Camentioning

confidence: 99%

Glycosphingolipid metabolism in cell fate specification

Russo

Capolupo

Loomba

et al. 2018

Journal of Cell Science

View full text Add to dashboard Cite

Glycosphingolipids (GSLs) are ubiquitous components of eukaryotic plasma membranes that consist of a ceramide backbone linked to a glycan moiety. Both the ceramide and the glycan parts of GSLs display structural variations that result in a remarkable repertoire of diverse compounds. This diversity of GSLs is exploited during embryogenesis, when different GSLs are produced at specific developmental stages and along several differentiation trajectories. Importantly, plasma membrane receptors interact with GSLs to modify their activities. Consequently, two otherwise identical cells can respond differently to the same stimulus owing to their different GSL composition. The metabolic reprograming of GSLs is in fact a necessary part of developmental programs, as its impairment results in developmental failure or tissue-specific defects. Moreover, single-cell variability is emerging as a fundamental player in development: GSL composition displays cell-to-cell variability in syngeneic cell populations owing to the regulatory gene expression circuits involved in microenvironment adaptation and in differentiation. Here, we discuss how GSLs are synthesized and classified and review the role of GSLs in the establishment and maintenance of cell identity. We further highlight the existence of the regulatory circuits that modify GSL pathways and speculate how GSL heterogeneity might contribute to developmental patterning.

show abstract

Glycosphingolipids of human embryonic stem cells

Cited by 23 publications

References 61 publications

Metabolic flux analysis of the neural cell glycocalyx reveals differential utilization of monosaccharides

Metabolic flux analysis of the neural cell glycocalyx reveals differential utilization of monosaccharides

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

Glycosphingolipid metabolism in cell fate specification

Contact Info

Product

Resources

About