title: Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination.
abstract: Multipotent neural stem cells (NSCs) provide a model to investigate neurogenesis and develop mechanisms of cell transplantation. In order to define improved markers of stemness and lineage specificity, we examined self-renewal and multi-lineage markers during long-term expansion and under neuronal and astrocyte differentiating conditions in human ESC-derived NSCs (hNSC H9 cells). In addition, with proteoglycans ubiquitous to the neural niche, we also examined heparan sulfate proteoglycans (HSPGs) and their regulatory enzymes. Our results demonstrate that hNSC H9 cells maintain self-renewal and multipotent capacity during extended culture and express HS biosynthesis enzymes and several HSPG core protein syndecans (SDCs) and glypicans (GPCs) at a high level. In addition, hNSC H9 cells exhibit high neuronal and a restricted glial differentiative potential with lineage differentiation significantly increasing expression of many HS biosynthesis enzymes. Furthermore, neuronal differentiation of the cells upregulated SDC4, GPC1, GPC2, GPC3 and GPC6 expression with increased GPC4 expression observed under astrocyte culture conditions. Finally, downregulation of selected HSPG core proteins altered hNSC H9 cell lineage potential. These findings demonstrate an involvement for HSPGs in mediating hNSC maintenance and lineage commitment and their potential use as novel markers of hNSC and neural cell lineage specification.
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Lotta E
authors.initials: LE
authors.lastname: Oikari
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Okolicsanyi
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Aro
authors.initials: A
authors.lastname: Qin
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Chieh
authors.initials: C
authors.lastname: Yu
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia. Electronic address: larisa.haupt@qut.edu.au.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
mesh_terms: D001253:Astrocytes / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000096:biosynthesis; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology
chemical_list: D015415:Biomarkers; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate
keywords: Differentiation; Glypican; Heparan sulfate proteoglycan; Neural stem cell; Syndecan