Dynamic Changes in Heparan Sulfate Nanostructure in Human Pluripotent Stem Cell Differentiation

Area of Science:

• Cell Biology
• Glycobiology
• Developmental Biology

Background:

• Heparan sulfate (HS) is a crucial cell-surface polysaccharide for mammalian development.
• Protein localization is known to affect signaling, but the role of polysaccharide nanostructure in signaling is unclear.

Purpose of the Study:

• To investigate the role of heparan sulfate nanostructure in human pluripotent stem cell (hPS) differentiation and growth factor signaling.
• To visualize HS distribution and nanostructure changes during differentiation using high-resolution imaging.

Main Methods:

• Utilized expansion microscopy (ExM) for high-resolution imaging of HS nanostructure.
• Correlated HS structural changes with fibroblast growth factor (FGF) signaling during hPS cell differentiation.

Main Results:

• Observed significant changes in HS nanostructure during hPS cell differentiation.
• Undifferentiated hPS cells showed hair-like HS protrusions that recruit FGF.
• Differentiated ectoderm lineage cells displayed HS in dispersed puncta, correlating with decreased FGF binding.

Conclusions:

• HS nanostructure, in addition to sequence, plays a critical role in modulating growth factor binding and signaling during cell differentiation.
• High-resolution glycan imaging with ExM is a powerful tool for studying HS structure-function relationships.