Extensive Determination of Glycan Heterogeneity Reveals an Unusual Abundance of High Mannose Glycans in Enriched Plasma Membranes of Human Embryonic Stem Cells

Abstract

Glycosylation is the process by which oligosaccharides, termed glycans, are appended onto membrane and secreted proteins and lipids. It is the most common and complex form of post-translational modification, with ϳ50% of all eukaryotic proteins glycosylated (1, 2). A majority of glycans are found on the cell surface, where they are optimally poised to be the first cellular components encountered by approaching cells, pathogens, antibodies, or other molecules, as well as advertise information about the internal state and homeostasis of the cell (3, 4). Therefore, glycans play an essential role in many biological processes, including cell development and differentiation, cell-cell or cell-matrix communication, and pathogen-host recognition (3,(5)(6)(7). In fact, differences in glycan profiles between healthy and diseased states are utilized for clinical diagnosis (7), providing targets for many novel classes of therapeutics including cancer chemotherapy, diabetes treatment, and antibiotic and anti-viral medicine (5, 8). Glycans are highly heterogeneous in nature, varying in the composition of individual monosaccharide building blocks, the positions with which these building blocks link to each other, and the stereochemical disposition of the linkages (␣ or ␤). This complexity has presented a significant challenge for obtaining structural information about glycans at the molecular From the

Regulation of Glycan Structures in Murine Embryonic Stem Cells

“…Although the striking abundance of high mannose N-glycans has been observed previously in human ES cells (111), the conversion to an equal abundance of complex structures following ES cell differentiation to both cell populations was an intriguing observation in the present study. The biochemical basis for this significant conversion in glycan character is unclear.…”

Adaptive immunity: the concept of linked functions

“…Embryo-specific antigens, eg., α-fetoprotein, have been known for a long time. The SSEA-1 antigen has been found on mouse embryo cells [30] and embryonic stem cells [31]. However, these are certainly not the antigens involved in the embryonic function of the immune system.…”

Cell Surface Sialylated N-Glycan Alterations during Development

“…High mannose-type N-glycans represent immature forms of N-glycans (65). In differentiated cells, the quantity of high mannose-type N-glycans decreases and complex/hybrid types of N-glycans start to appear in abundance (61,66,88).…”