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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
Statement of
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
Cells, Cultured
Mice, Transgenic
Intermediate Filament Proteins
Ubiquitin Thiolesterase
Nerve Tissue Proteins
Cell Differentiation
Cell Proliferation
Cell Aggregation
Cell Polarity
Cell Shape
Protein Transport
Embryonic Stem Cells
DOI: 10.1091/mbc.E08-06-0596
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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