title: Regulation of oligodendrocyte precursor maintenance by chondroitin sulphate glycosaminoglycans.
abstract: Chondroitin sulfate proteoglycans (CSPGs) have been proven to inhibit morphological maturation of oligodendrocytes as well as their myelination capabilities. Yet, it remained unclear, whether CSPGs and/or their respective chondroitin sulfate glycosaminoglycan (CS-GAG) side chains also regulate the oligodendrocyte lineage progression. Here, we initially show that CS-GAGs detected by the monoclonal antibody 473HD are expressed by primary rat NG2-positive oligodendrocyte precursor cells (OPCs) and O4-positive immature oligodendrocytes. CS-GAGs become down-regulated with ongoing oligodendrocyte differentiation. Enzymatic removal of the CS-GAG chains by the bacterial enzyme Chondroitinase ABC (ChABC) promoted spontaneous differentiation of proliferating rat OPCs toward O4-positive immature oligodendrocytes. Upon forced differentiation, the enzymatic removal of the CS-GAGs accelerated oligodendrocyte differentiation toward both MBP-positive and membrane forming oligodendrocytes. These processes were attenuated on enriched CSPG fractions, mainly consisting of Phosphacan/RPTPβ/ζ and to less extent of Brevican and NG2. To qualify CS-GAGs as universal regulators of oligodendrocyte biology, we finally tested the effect of CS-GAG removal on OPCs from different sources such as mouse cortical oligospheres, mouse spinal cord neurospheres, and most importantly human-induced pluripotent stem cell-derived radial glia-like neural precursor cells. For all culture systems used, we observed a similar inhibitory effect of CS-GAGs on oligodendrocyte differentiation. In conclusion, this study clearly suggests an important fundamental principle for complex CS-GAGs to regulate the oligodendrocyte lineage progression. Moreover, the use of ChABC in order to promote oligodendrocyte differentiation toward myelin gene expressing cells might be an applicable therapeutic option to enhance white matter repair.
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.|International Graduate School of Neuroscience, Ruhr-University Bochum, Bochum, Germany.|Institute of Reconstructive Neurobiology, LIFE&BRAIN Center, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Karus
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Ulc
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Ehrlich
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.|International Graduate School of Neuroscience, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Czopka
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.|International Graduate School of Neuroscience, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hennen
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE&BRAIN Center, Bonn, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE&BRAIN Center, Bonn, Germany.
authors.forename: Marija
authors.initials: M
authors.lastname: Mizhorova
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Naila
authors.initials: N
authors.lastname: Qamar
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE&BRAIN Center, Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Faissner
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism*; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: C038142:chondroitin sulfate glycosaminoglycan; D002809:Chondroitin Sulfates; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D019765:Chondroitin ABC Lyase
keywords: chondroitinase ABC; extracellular matrix; lectican; oligodendrocyte differentiation