Glycans in stem cell regulation: from Drosophila tissue stem cells to mammalian pluripotent stem cells

Abstract

Cell surface glycans, which are tissue-specific and developmentally regulated, work as essential modulators in ligand-receptor interactions, binding to various signal ligands including Wnt, Hedgehog, fibroblast growth factors, epidermal growth factors, and bone morphogenetic proteins, as well as in cell-cell interactions and cell-extracellular matrix interactions. These signals are essential for the stemness and differentiation of various kinds of stem cells. In addition, the intracellular O-linked N-acetylglucosamine, a form of glycosylation found only on nuclear or cytoplasmic proteins, regulates core transcription factors of stemness and phosphorylation of downstream signal components. Therefore, various kinds of glycans regulate the stem cell status; the structures of many of which are evolutionarily conserved from Drosophila to mammals. Understanding the molecular mechanisms of glycans in stemness and differentiation is increasingly important for innovative clinical applications, as well as for basic research. This Review focuses on the roles of glycans in Drosophila tissue stem cells and mammalian pluripotent stem cells.

Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer

“…The basis for these differences is unclear; however, it is notable that there is a remodeling of the overall O-glycan structures in the absence of α4GnT (Karasawa et al, 2012), whereas the simple glycan structure Tn antigen dominates in the absence of C1GalT1 . These differences in O-glycosylation profiles may fundamentally alter cell-intrinsic functions, for example those of stem cells (Nishihara, 2018). Further, we observed the effect of C1galt1 loss impacts the entire gland epithelium, whereas α4GnT deficiency impacts the deep gland (where Muc6 is expressed; Karasawa et al, 2012).…”

Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging

“…The presence of glycans determines the structure, stability, and localization of glycoproteins, which affect a wide variety of biological processes, such as development (Haltiwanger & Lowe, 2004), tumorigenesis (Ohtsubo & Marth, 2006) and inflammation (Varki & Gagneux, 2015). Glycans are required for stem cell regulations by modulating signaling molecules that govern self‐renewal and differentiation of stem cells (Nishihara, 2018). As glycans are located at the cell surface, they have been utilized as biomarkers, for example, pluripotent status of mouse embryonic stem cells (Adewumi et al, 2007; Muramatsu & Muramatsu, 2004; Muramatsu & Muramatsu, 2004) and human induced pluripotent stem cells (Tateno et al, 2011).…”

Mucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis

“…It is becoming clear that glycosylation acts as a pivotal regulatory switch of pluripotency in a range of cell types in different organisms (Nishihara, 2018). In the present study, we characterized the function of mucin-type O-glycosylation in the pluripotency.…”