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    Specification of murine ground state pluripotent stem cells to regional neuronal populations

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    Author
    Alsanie, WF; Niclis, JC; Hunt, CP; De Luzy, IR; Penna, V; Bye, CR; Pouton, CW; Haynes, J; Firas, J; Thompson, LH; ...
    Date
    2017-11-22
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    de Luzy, Isabelle; Parish, Clare; Alsanie, Walaa; Hunt, Cameron; Penna, Vanessa; NICLIS, JONATHAN; Bye, Chris; POUTON, COLIN; Thompson, Lachlan
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Anatomy and Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Alsanie, W. F., Niclis, J. C., Hunt, C. P., De Luzy, I. R., Penna, V., Bye, C. R., Pouton, C. W., Haynes, J., Firas, J., Thompson, L. H. & Parish, C. L. (2017). Specification of murine ground state pluripotent stem cells to regional neuronal populations. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/s41598-017-16248-x.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255466
    DOI
    10.1038/s41598-017-16248-x
    Abstract
    Pluripotent stem cells (PSCs) are a valuable tool for interrogating development, disease modelling, drug discovery and transplantation. Despite the burgeoned capability to fate restrict human PSCs to specific neural lineages, comparative protocols for mouse PSCs have not similarly advanced. Mouse protocols fail to recapitulate neural development, consequently yielding highly heterogeneous populations, yet mouse PSCs remain a valuable scientific tool as differentiation is rapid, cost effective and an extensive repertoire of transgenic lines provides an invaluable resource for understanding biology. Here we developed protocols for neural fate restriction of mouse PSCs, using knowledge of embryonic development and recent progress with human equivalents. These methodologies rely upon naïve ground-state PSCs temporarily transitioning through LIF-responsive stage prior to neural induction and rapid exposure to regional morphogens. Neural subtypes generated included those of the dorsal forebrain, ventral forebrain, ventral midbrain and hindbrain. This rapid specification, without feeder layers or embryoid-body formation, resulted in high proportions of correctly specified progenitors and neurons with robust reproducibility. These generated neural progenitors/neurons will provide a valuable resource to further understand development, as well disorders affecting specific neuronal subpopulations.

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