Cell Surface N-Glycans Influence Electrophysiological Properties and Fate Potential of Neural Stem Cells

Summary Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood. We tested the hypothesis that cell surface carbohydrates contribute to NSPC membrane capacitance and fate. We found NSPCs differing in fate potential express distinct patterns of glycosylation enzymes. Screening several glycosylation pathways revealed that the one forming highly branched N-glycans differs between neurogenic and astrogenic populations of cells in vitro and in vivo. Enhancing highly branched N-glycans on NSPCs significantly increases membrane capacitance and leads to the generation of more astrocytes at the expense of neurons with no effect on cell size, viability, or proliferation. These data identify the N-glycan branching pathway as a significant regulator of membrane capacitance and fate choice in the neural lineage.
Highlights • Biophysical property membrane capacitance reflects fate bias in the neural lineage • N-Glycan branching identifies cells with different fates in vitro and in vivo • N-Glycan branching accounts for capacitance differences reflecting fate • Branching affects fate, leading to more differentiated astrocytes and fewer neurons
Flanagan and colleagues tested glycosylation contributions to a unique, fate-specific electrophysiological property of neural stem cells. They found the N-glycan branching pathway generating highly branched N-glycans associated with astrocyte fate. Enhanced branching shifted the electrophysiological property and fate potential of neural stem cells toward astrocytes, revealing the importance of N-glycan branching to neural stem cell differentiation.