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USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors

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Taylor,  Verdon
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Jolly, L. A., Taylor, V., & Wood, S. A. (2009). USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors. Molecular Biology of the Cell, 20, 2015-2029.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8F77-6
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, β-catenin, and AF-6) and apical markers (Prominin1, atypical protein kinase C-ζ) 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: βIII-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.