HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes
Description
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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ID Code: | 202174 | ||||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||||
Refereed: | Yes | ||||||||
ORCID iD: |
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Measurements or Duration: | 27 pages | ||||||||
Keywords: | BDNF, heparan sulfate proteoglycans, neural stem cells, PDGF-B, RRID:AB_10671920, RRID:AB_2099233, RRID:AB_2286686, RRID:AB_2286949, RRID:AB_2340852, RRID:AB_2801499, RRID:AB_2827641, RRID:AB_306716, RRID:AB_330924, RRID:AB_443209, RRID:AB_444319, RRID:AB_446723, RRID:AB_561053, RRID:AB_631776, RRID:AB_776175, RRID:AB_92588, RRID:AB_92643 | ||||||||
DOI: | 10.1002/jnr.24666 | ||||||||
ISSN: | 0360-4012 | ||||||||
Pure ID: | 63430476 | ||||||||
Divisions: | Current > Research Centres > Centre for Genomics and Personalised Health Past > Institutes > Institute of Health and Biomedical Innovation Current > QUT Faculties and Divisions > Faculty of Health |
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Funding Information: | The authors acknowledge the support of members of the Genomics Research Centre and the Cell Analysis Facility at IHBI-QUT. This study was supported by a QUT Postgraduate Award stipend (LEO), and initial funding support from the Estate of the late Clem Jones, AO (LMH and LRG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | ||||||||
Copyright Owner: | 2020 Wiley Periodicals, Inc | ||||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||||
Deposited On: | 17 Jul 2020 03:07 | ||||||||
Last Modified: | 14 Jun 2024 22:54 |
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