Regulation of Glycan Structures in Murine Embryonic Stem Cells

Abstract

Background: Glycans contribute to vertebrate development, but regulatory mechanisms are unknown. Results: Glycans and transcripts encoding the glycosylation machinery were profiled during stem cell differentiation. Conclusion: Changes in glycans frequently correlated with changes in transcripts, supporting a significant role for transcriptional regulation. Significance: Knowledge of the mechanisms that regulate glycan expression provides insight into the roles of glycosylation in development.

Glycosylation and stem cells: Regulatory roles and application of iPSCs in the study of glycosylation‐related disorders

“…Increased expression of FUT1 and FUT2 genes, which encode enzymes that catalyze the linkage between fucose and its acceptor protein through an α1-2 linkage, accounts for elevated fucosylation although other regulatory steps are likely to contribute as well [25, 30, 32, 34, 43, 44]. These findings contrast with previous studies in murine PSCs where α1-2 fucosylation is not prevalent, highlighting potential differences in glycosylation patterns between the two species [13, 33]. Alternatively, rather than being indicative of differences at the species level this apparent conflict may indicate that ‘naive’ (murine ESCs) and ‘primed’ PSCs (human ESCs) have a different cell surface glycome, consistent with the earlier work of Nash and co-workers [29].…”

“…More recently however, the development of human stem cell-based systems and a new generation of genome editing technologies has greatly accelerated our understanding in this area. Likewise, the advent of modern glycomics and the optimization of techniques such as mass spectrometry [13, 14], capillary electrophoresis [15], and liquid chromatography [16] have made it possible to rapidly profile the glycan diversity in cells and tissues (Fig. 2).…”

“…The increased relative abundance of high mannose glycans, which represent up to 85% of the total N-glycome in PSCs, may reflect the expansion of the ER in these cells or decreased processing within the Golgi [18, 21, 22, 35]. The latter is less likely based on the transcript abundance analysis of mouse ES cells and differentiated lineages which shows equivalent expression of many glycosyltransferases involved in early N-glycan processing [13]. …”

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

“…The biosynthesis of glycans is an intricate process requiring the coordinated action of multiple glycosyltransferases and glycosidases to synthesize discrete structures (Cummings and Pierce, 2014; Moremen et al, 2012). There is currently little understanding of how glycan biosynthesis is controlled (Nairn et al, 2012) or which enzymes are important in the biosynthesis of specific epitopes underlying clinical pathologies, hindering the development of glycosylation-based therapeutic strategies (Dalziel et al, 2014; Dube and Bertozzi, 2005). Here we have taken a systematic, multi-disciplinary approach to identify glycomic changes and the underlying glycosyltransferases associated with melanoma metastasis in patient samples.…”

Multi-level regulation of cellular glycosylation: from genes to transcript to enzyme to structure

“…A number of investigators have attempted to relate transcript levels to glycoenzyme activity and carbohydrate structures, including the response of the system to perturbations [11,24–26]. Such studies have been conducted using human promyelocytic leukocytes differentiated to primary neutrophils [24], a limited panel of mouse tissue [11], mouse embryonic stem cells differentiated to embryoid bodies and endodermal cells [25], and epithelial ovarian cancer cell types [26]. The broad conclusion of these studies is that glycogene, and more specifically glycosyltransferase, expression measurements in a number of cases can semi-quantitatively predict corresponding enzyme activity and cell-surface glycan expression.…”