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

doi:10.1016/j.stemcr.2018.08.011

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

Stem Cell Reports. 2018 Oct 9;11(4):869-882. doi: 10.1016/j.stemcr.2018.08.011. Epub 2018 Sep 6.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
⁶ 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.
⁷ 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.
⁸ 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. Electronic address: lisa.flanagan@uci.edu.

Abstract

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acetylglucosamine / metabolism
Animals
Astrocytes / cytology
Brain / cytology
Cell Differentiation
Cell Lineage*
Cell Membrane / metabolism*
Cell Proliferation
Cell Size
Cell Survival
Electrophysiological Phenomena*
Fucose / metabolism
Gene Expression Regulation
Glycosylation
Mice
N-Acetylneuraminic Acid / metabolism
Neural Stem Cells / cytology*
Neural Stem Cells / metabolism*
Neurogenesis
Polysaccharides / metabolism*
Stem Cell Niche

Substances

Polysaccharides
Fucose
N-Acetylneuraminic Acid
Acetylglucosamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding