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https://hdl.handle.net/2440/51549
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DC Field | Value | Language |
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dc.contributor.author | Jolly, L. | - |
dc.contributor.author | Taylor, V. | - |
dc.contributor.author | Wood, S. | - |
dc.contributor.editor | Bronner-Fraser, M. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Molecular Biology of the Cell, 2009; 20(7):2015-2029 | - |
dc.identifier.issn | 1059-1524 | - |
dc.identifier.issn | 1939-4586 | - |
dc.identifier.uri | http://hdl.handle.net/2440/51549 | - |
dc.description.abstract | The substrate-specific deubiquitylating enzyme USP9X is a putative “stemness” gene expressed in many progenitor cell populations. To test its function in embryonic stem cell-derived neural progenitor/stem cells, we expressed USP9X from a Nestin promoter. Elevated USP9X levels resulted in two phenomena. First, it produced a dramatically altered cellular architecture wherein the majority (>80%) of neural progenitors was arranged into radial clusters. These progenitors expressed markers of radial glial cells and were highly polarized with adherens junction proteins (N-cadherin, -catenin, and AF-6) and apical markers (Prominin1, atypical protein kinase C-) as well as Notch, Numb, and USP9X itself, concentrated at the center. The cluster centers were also devoid of nuclei and so resembled the apical end-feet of radial progenitors in the neural tube. Second, USP9X overexpression caused a fivefold increase in the number of radial progenitors and neurons, in the absence of exogenous growth factors. 5-Bromo-2-deoxyuridine labeling, as well as the examination of the brain lipid-binding protein:III-tubulin ratio, indicated that nestin-USP9X enhanced the self-renewal of radial progenitors but did not block their subsequent differentiation to neurons and astrocytes. nestin-USP9X radial progenitors reformed clusters after passage as single cells, whereas control cells did not, suggesting it aids the establishment of polarity. We propose that USP9X-induced polarization of these neural progenitors results in their radial arrangement, which provides an environment conducive for self-renewal. | - |
dc.description.statementofresponsibility | Lachlan A. Jolly, Verdon Taylor and Stephen A. Wood | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Cell Biology | - |
dc.source.uri | http://dx.doi.org/10.1091/mbc.e08-06-0596 | - |
dc.subject | Prosencephalon | - |
dc.subject | Astrocytes | - |
dc.subject | Neurons | - |
dc.subject | Cells, Cultured | - |
dc.subject | Animals | - |
dc.subject | Mice, Transgenic | - |
dc.subject | Mice | - |
dc.subject | Intermediate Filament Proteins | - |
dc.subject | Ubiquitin Thiolesterase | - |
dc.subject | Endopeptidases | - |
dc.subject | Nerve Tissue Proteins | - |
dc.subject | Cell Differentiation | - |
dc.subject | Cell Proliferation | - |
dc.subject | Cell Aggregation | - |
dc.subject | Cell Polarity | - |
dc.subject | Cell Shape | - |
dc.subject | Protein Transport | - |
dc.subject | Embryonic Stem Cells | - |
dc.subject | Nestin | - |
dc.subject | Biomarkers | - |
dc.title | USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1091/mbc.E08-06-0596 | - |
dc.relation.grant | NHMRC | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Jolly, L. [0000-0003-4538-2658] | - |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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