Abstract
Heparan sulfate proteoglycans (HSPGs) are an evolutionarily ancient subclass of glycoproteins with exquisite structural complexity. They are ubiquitously expressed across tissues and have been found to exert a multitude of effects on cell behavior and the surrounding microenvironment. Evidence has shown that heterogeneity in HSPG composition is crucial to its functions as an essential scaffolding component in the extracellular matrix as well as a vital cell surface signaling co-receptor. Here, we provide an overview of the significance of HSPGs as essential regulators of stem cell function. We discuss the various roles of HSPGs in distinct stem cell types during key physiological events, from development through to tissue homeostasis and regeneration. The contribution of aberrant HSPG production to altered stem cell properties and dysregulated cellular homeostasis characteristic of cancer is also reviewed. Finally, we consider approaches to better understand and exploit the multifaceted functions of HSPGs in influencing stem cell characteristics for cell therapy and associated culture expansion strategies.
Highlights
The glycocalyx is a dense layer of glycoproteins and glycolipids that coats the exterior of the cell membrane
Heparan sulfate proteoglycans (HSPGs) have emerged as key mediators of stem cell function, essential for the regulation of development, homeostasis and regeneration
Evidence from embryonic stem cell (ESC) studies highlighted the significance of HSPGs and their biosynthetic machinery in mediating key lineage commitment and cell fate decisions
Summary
The glycocalyx is a dense layer of glycoproteins and glycolipids that coats the exterior of the cell membrane. It is comprised of a variety of polysaccharides covalently attached to lipids or proteins, and functions as an essential interface between external and internal cellular environments. The base structure of HS is highly conserved throughout multicellular organisms, including mammals, fruit flies (Drosophila melanogaster) (Nakato et al, 1995), nematodes (Caenorhabditis elegans) (Townley and Bülow, 2011) and hydra (Hydra Magnipapillata and Hydra vulgaris) (Sarras et al, 1991; Yamada et al, 2007), indicating an ancient evolutionary origin. HS chains are covalently attached to core proteins belonging
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