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

Andrew R. Yale; Jamison L. Nourse; Kayla R. Lee; Syed N. Ahmed; Janahan Arulmoli; Alan Y.L. Jiang; Lisa P. McDonnell; Giovanni A. Botten; Abraham P. Lee; Edwin S. Monuki; Michael Demetriou; Lisa A. Flanagan

Stem Cell Reports (Oct 2018)

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

Andrew R. Yale,
Jamison L. Nourse,
Kayla R. Lee,
Syed N. Ahmed,
Janahan Arulmoli,
Alan Y.L. Jiang,
Lisa P. McDonnell,
Giovanni A. Botten,
Abraham P. Lee,
Edwin S. Monuki,
Michael Demetriou,
Lisa A. Flanagan

Affiliations

Andrew R. Yale: Department of Anatomy & Neurobiology, University of California, Irvine, Irvine, CA 92697, USA; Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA
Jamison L. Nourse: Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA
Kayla R. Lee: Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA
Syed N. Ahmed: Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA
Janahan Arulmoli: Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA
Alan Y.L. Jiang: Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA
Lisa P. McDonnell: Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA
Giovanni A. Botten: Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
Abraham P. Lee: Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA
Edwin S. Monuki: Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA
Michael Demetriou: Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA
Lisa A. Flanagan: Department of Anatomy & Neurobiology, University of California, Irvine, Irvine, CA 92697, USA; Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA; Corresponding author

Journal volume & issue: Vol. 11, no. 4
pp. 869 – 882

Abstract

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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. : 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. Keywords: neuron progenitor, astrocyte progenitor, glycosylation, biophysical, dielectrophoresis, membrane capacitance, mouse, branch, MGAT, L-PHA

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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