Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/51549
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Type: Journal article
Title: USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors
Author: Jolly, L.
Taylor, V.
Wood, S.
Citation: Molecular Biology of the Cell, 2009; 20(7):2015-2029
Publisher: Amer Soc Cell Biology
Issue Date: 2009
ISSN: 1059-1524
1939-4586
Statement of
Responsibility: 
Lachlan A. Jolly, Verdon Taylor and Stephen A. Wood
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.
Keywords: Prosencephalon
Astrocytes
Neurons
Cells, Cultured
Animals
Mice, Transgenic
Mice
Intermediate Filament Proteins
Ubiquitin Thiolesterase
Endopeptidases
Nerve Tissue Proteins
Cell Differentiation
Cell Proliferation
Cell Aggregation
Cell Polarity
Cell Shape
Protein Transport
Embryonic Stem Cells
Nestin
Biomarkers
DOI: 10.1091/mbc.E08-06-0596
Grant ID: NHMRC
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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