TABLE 1.
Phenotypes of proteoglycan-deficient stem cells.
| Cell type | Proteoglycans affected | Phenotype | Mechanism | (References) |
|---|---|---|---|---|
| Ext-1 −/− ESCs | HSPGs | When cultured with no or low concentration of leukaemia inhibitory factor (LIF), Ext-1 −/− ESCs maintained the typical morphology of ESCs, high ALP activity and high expression of the pluripotency gene Nanog and were unable to exit from self-renewal | FGF and BMP signaling | (Kraushaar et al., 2010, 2012) |
| GlcAT-I −/− ESCs | HSPGs, CSPGs, DSPGs | GlcAT-I −/− ESCs failed to initiate differentiation and showed higher expression of two pluripotency genes Nanog and Sox2 than GlcAT-I +/- ESCs and GlcAT-I +/+ ESCs | CS colocalizes with and binds to E-cadherin | Izumikawa et al. (2014) |
| Ndst1/2 −/− ESCs | Sulfated proteoglycans | Ndst1/2 −/− ESCs can take the initial step toward differentiation into all three germ layers but were arrested in a primitive ectoderm and/or endoderm stage | FGF signaling | Lanner et al. (2010); Forsberg et al. (2012) |
| Ndst1/2 −/− ESCs blocked differentiation and were maintained in a naïve state | FGF4 signaling | |||
| Ext-1 knockdown cancer stem cells | HSPGs | Knockdown of Ext-1 in MCF7/ADR cells significantly reduced cancer stem cell markers, mammosphere number and the colony formation ability | FGF4 signaling | Manandhar et al. (2017) |
| Ext-1 −/− prostate stem/progenitor cells (PrSCs) | HSPGs | Deletion of Ext-1 in PrSCs disrupted their ability to self-renew and attenuated prostate regeneration | TGF-β signaling | Rai et al. (2020) |
| Surfen treated ESCs | HSPGs | Surfen treated ESCs were arrested in their pluripotent state due to decreased binding sites for growth factors within their GAG chains | FGF2/MAPK, RTK, and VEGF signaling | Huang et al. (2018b) |
HSPGs, heparan sulfate proteoglycans; CSPGs, chondroitin sulfate proteoglycans; DSPGs, dermatan sulfate proteoglycans; FGF, fibroblast growth factor; BMP, bone morphogenetic protein; FGF4, fibroblast growth factor 4; FGF2, fibroblast growth factor 2; TGF-β, transforming growth factor-β; MAPK, mitogen-activated protein kinase; RTK, receptor tyrosine kinase; VEGF, vascular endothelial growth factor.