Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation.

Autor:	Yale AR; Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA 92697, USA; Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Kim E; Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Gutierrez B; Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA 92697, USA; Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Hanamoto JN; Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Lav NS; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Nourse JL; Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Salvatus M; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Hunt RF; Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA., Monuki ES; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA; Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA 92697, USA., Flanagan LA; Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA 92697, USA; Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Sue and 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.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2023 Jun 13; Vol. 18 (6), pp. 1340-1354. Date of Electronic Publication: 2023 May 11.
DOI:	10.1016/j.stemcr.2023.04.007
Abstrakt:	Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. Competing Interests: Conflict of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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