HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes.

Oikari, LE; Yu, C; Okolicsanyi, RK; Avgan, N; Peall, IW; Griffiths, LR; Haupt, LM

HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes.

Oikari, LE Yu, C Okolicsanyi, RK Avgan, N Peall, IW Griffiths, LR Haupt, LM

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Journal of neuroscience research, 2020, 98, (8), pp. 1619-1645
Issue Date:: 2020-08

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Field	Value	Language
dc.contributor.author	Oikari, LE
dc.contributor.author	Yu, C
dc.contributor.author	Okolicsanyi, RK
dc.contributor.author	Avgan, N
dc.contributor.author	Peall, IW
dc.contributor.author	Griffiths, LR
dc.contributor.author	Haupt, LM
dc.date.accessioned	2020-12-16T00:37:19Z
dc.date.available	2020-05-14
dc.date.available	2020-12-16T00:37:19Z
dc.date.issued	2020-08
dc.identifier.citation	Journal of neuroscience research, 2020, 98, (8), pp. 1619-1645
dc.identifier.issn	0360-4012
dc.identifier.issn	1097-4547
dc.identifier.uri	http://hdl.handle.net/10453/144734
dc.description.abstract	Generating neurons from human stem cells has potential for brain damage therapy and neurogenesis modeling, but current efficacy is limited by culture heterogeneity and the lack of markers. We have previously reported the heparan sulfate proteoglycans (HSPGs) glypican-1 (GPC1) and -4 (GPC4) as the markers of lineage-specific human neural stem cells (hNSCs) and mediators of hNSC lineage potential. Here, we further examined phenotypical characteristics and GPC1 and GPC4 during neural differentiation of hNSCs in the presence of two neurogenic growth factors reported to bind to heparan sulfate: brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor-B (PDGF-B). In hNSC neural cultures, GPC1 and GPC4 were expressed along neurites and cell bodies in long-term (40-60 days) neural differentiation cultures demonstrating the areas of differential localization-suggesting potentially different functions. Neural differentiation cultures in the presence of BDNF or PDGF-B generated phenotypically different neural cells with BDNF treatment associated with higher GPC4 versus GPC1 expression, increased heterogeneity, and differential neuron subtype marker expression to PDGF-B cultures. PDGF-B cultures exhibited higher levels of spontaneous activity and reduced heterogeneity over long-term culture associated with decreased GPC4. Untreated neural cultures were highly variable, supporting the use of neuroregulatory growth factors for guided differentiation. Targeted siRNA downregulation of GPC1/4 reduced neural differentiation markers and altered response to exogenous BDNF and PDGF-B. This work confirms GPC1 and GPC4 as regulators of human neural differentiation and supports their use as novel markers of neural cell characterization.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation.ispartof	Journal of neuroscience research
dc.relation.isbasedon	10.1002/jnr.24666
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	1109 Neurosciences, 1701 Psychology
dc.subject.classification	Neurology & Neurosurgery
dc.title	HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes.
dc.type	Journal Article
utslib.citation.volume	98
utslib.location.activity	United States
utslib.for	1109 Neurosciences
utslib.for	1701 Psychology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2020-12-16T00:37:05Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	98
utslib.citation.issue	8

Abstract:

Generating neurons from human stem cells has potential for brain damage therapy and neurogenesis modeling, but current efficacy is limited by culture heterogeneity and the lack of markers. We have previously reported the heparan sulfate proteoglycans (HSPGs) glypican-1 (GPC1) and -4 (GPC4) as the markers of lineage-specific human neural stem cells (hNSCs) and mediators of hNSC lineage potential. Here, we further examined phenotypical characteristics and GPC1 and GPC4 during neural differentiation of hNSCs in the presence of two neurogenic growth factors reported to bind to heparan sulfate: brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor-B (PDGF-B). In hNSC neural cultures, GPC1 and GPC4 were expressed along neurites and cell bodies in long-term (40-60 days) neural differentiation cultures demonstrating the areas of differential localization-suggesting potentially different functions. Neural differentiation cultures in the presence of BDNF or PDGF-B generated phenotypically different neural cells with BDNF treatment associated with higher GPC4 versus GPC1 expression, increased heterogeneity, and differential neuron subtype marker expression to PDGF-B cultures. PDGF-B cultures exhibited higher levels of spontaneous activity and reduced heterogeneity over long-term culture associated with decreased GPC4. Untreated neural cultures were highly variable, supporting the use of neuroregulatory growth factors for guided differentiation. Targeted siRNA downregulation of GPC1/4 reduced neural differentiation markers and altered response to exogenous BDNF and PDGF-B. This work confirms GPC1 and GPC4 as regulators of human neural differentiation and supports their use as novel markers of neural cell characterization.

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http://hdl.handle.net/10453/144734