Sulfation of glycosaminoglycans modulates the cell cycle of embryonic mouse spinal cord neural stem cells

  • In the developing spinal cord neural stem and progenitor cells (NSPCs) secrete and are surrounded by extracellular matrix (ECM) molecules that influence their lineage decisions. The chondroitin sulfate proteoglycan (CSPG) DSD-1-PG is an isoform of receptor protein tyrosine phosphatase-beta/zeta (RPTP\(\beta\)/\(\zeta\)), a \(\it trans-\)membrane receptor expressed by NSPCs. The chondroitin sulfate glycosaminoglycan chains are sulfated at distinct positions by sulfotransferases, thereby generating the distinct DSD-1-epitope that is recognized by the monoclonal antibody (mAb) 473HD. We detected the epitope, the critical enzymes and RPTP\(\beta\)/\(\zeta\) in the developing spinal cord. To obtain insight into potential biological functions, we exposed spinal cord NSPCs to sodium chlorate. The reagent suppresses the sulfation of glycosaminoglycans, thereby erasing any sulfation code expressed by the glycosaminoglycan polymers. When NSPCs were treated with chlorate and cultivated in the presence of FGF2, their proliferation rate was clearly reduced, while NSPCs exposed to EGF were less affected. Time-lapse video microscopy and subsequent single-cell tracking revealed that pedigrees of NSPCs cultivated with FGF2 were strongly disrupted when sulfation was suppressed. Furthermore, the NSPCs displayed a protracted cell cycle length. We conclude that the inhibition of sulfation with sodium chlorate interferes with the FGF2-dependent cell cycle progression in spinal cord NSPCs.

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Metadaten
Author:Elena SchabergGND, Ursula TheocharidisGND, Marcus MayORCiDGND, Katrin LessmannGND, Timm SchroederGND, Andreas FaissnerORCiDGND
URN:urn:nbn:de:hbz:294-83730
DOI:https://doi.org/10.3389/fcell.2021.643060
Parent Title (English):Frontiers in cell and developmental biology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Language:English
Date of Publication (online):2021/10/12
Date of first Publication:2021/06/08
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
chondroitin sulfate proteoglycan; extracellular matrix; single-cell tracking; sodium chlorate; spinal cord; stem cell niche; sulfation
Volume:9
Issue:Article 643060
First Page:643060-1
Last Page:643060-14
Note:
Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Lehrstuhl für Zellmorphologie und Molekulare Neurobiologie
open_access (DINI-Set):open_access
faculties:Fakultät für Biologie und Biotechnologie
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International