Embryoglycan: a highly branched poly-N-acetyllactosamine in pluripotent stem cells and early embryonic cells

Abstract

Embryonal carcinoma cells, stem cells of teratocarcinomas, are pluripotent stem cells and also prototypes of embryonic stem cells. Embryonal carcinoma cells contain large amounts of a highly branched poly-N-acetyllactosamine called embryoglycan, which has a molecular weight of approximately 10,000 or greater, and is asparagine-linked. This glycan was found by analyses of fucose-labeled glycopeptides, and its characteristics were established by biochemical analyses. The content of embryoglycan progressively decreases during the in vitro differentiation of embryonal carcinoma cells. Embryoglycan is also abundant in mouse embryonic stem cells and preimplantation mouse embryos, and decreases during embryogenesis. Embryoglycan carries a number of carbohydrate markers of murine pluripotent stem cells. Lewis x markers, such as SSEA-1, 4C9 antigen, and binding sites for Lotus tetragonolobus agglutinin are of particular importance. 4C9 antigenicity requires clustering of Lewis x, best accomplished by poly-N-acetyllactosamine branching, whereas SSEA-1 does not. Although in vivo evidence is lacking, these epitopes have been suggested to participate in cell-to-cell and cell-to-substratum adhesion. Other markers on embryoglycan include α-galactosyl antigens such as ECMA-2, and binding sites for Dolichos biflorus agglutinin, the epitope of which is considered to be identical to Sd antigen, namely, GalNAcβ1-4(NeuAcα2-3)Galβ1-4GlcNAc. While embryoglycan is also present in human teratocarcinoma cells, the carbohydrate markers characterized in human pluripotent stem cells to date are largely carried by glycolipids and keratan sulfate. Information on embryoglycan and markers carried by it may assist in the development of new markers of human pluripotent stem cells and their progenies.

Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives

“…1D ). As expected, Ssea1 a cell surface protein associated with undifferentiated ESCs 8 , was expressed in both undifferentiated SCR and KD ESCs. Confocal imaging of permeabilized and non-permeablized SCR ESCs, further confirmed the localization of MAGEB16 in cytosol and the cell plasma membrane (supplementary Figure 1E ).…”

Induction of specific adaptive immune responses by immunization with newly designed artificial glycosphingolipids

“…sLe X is expressed on lymphocytes and in gastrointestinal tumors 16–18 and exhibits adhesive properties that play a role in the metastasis of these cancers. Le X , also known as SSEA-1, is a precursor of sLe X and a well-characterized cell surface marker of mouse embryo and stem cells 19 . Core fucose forms the core structure of N -linked oligosaccharides in mammalian glycoproteins such as α-fetoprotein isoform AFP-L3, a hepatocellular carcinoma–specific antigen 15 .…”

Keratan sulfate, a complex glycosaminoglycan with unique functional capability

“…A further KS type (type III) has been identified in the PNS/CNS attached via an O -linked 2- O mannose residue to serine residues on proteoglycan core proteins but is antigenically distinct from KS-I and KS-II ( Funderburgh 2002 ) (Figure 1 ). A related mucin-like polylactosamine molecule, embryoglycan, has also been described which bears some similarities to minimally sulfated embryonic KS chains but is a highly branched molecule whereas KS-I is a linear molecule ( Muramatsu 2017 ).…”

“…A related bi-, tri- or higher antennary branched 120–440 kDa proteoglycan composed of a complex core polylactosamine assembled from β1–3-linked d -GlcNAc and d -Gal units has also been observed on embryonic cells ( Dvorak et al 1998 ; Muramatsu 2017 ). Embryoglycan carries a number of developmentally regulated glycan marker molecules such as the trisaccharide Gal(β1→4)-[Fuc(α1→3)] GlcNAc Lewis X epitope, also known as CD15/SSEA-1 (stage-specific embryonic antigen) ( Son et al 2009 ), a cell surface marker of embryonic stem cells, embryonal carcinoma cells and multipotential cells of early embryos ( Muramatsu and Muramatsu 2004 ).…”