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    A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells

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    Author
    Niclis, JC; Gantner, CW; Hunt, CPJ; Kauhausen, JA; Durnall, JC; Haynes, JM; Pouton, CW; Parish, CL; Thompson, LH
    Date
    2017-09-12
    Source Title
    Stem Cell Reports
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Parish, Clare; Gantner, Carlos William Baevski; Thompson, Lachlan; Kauhausen, Jessica
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Anatomy and Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Niclis, J. C., Gantner, C. W., Hunt, C. P. J., Kauhausen, J. A., Durnall, J. C., Haynes, J. M., Pouton, C. W., Parish, C. L. & Thompson, L. H. (2017). A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells. STEM CELL REPORTS, 9 (3), pp.868-882. https://doi.org/10.1016/j.stemcr.2017.08.002.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256841
    DOI
    10.1016/j.stemcr.2017.08.002
    Abstract
    Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic. These findings highlight the promise of stem cell-based procedures for anatomically correct reconstruction of specific neuronal pathways but also emphasize the scope for further refinement in order to limit the inclusion of uncharacterized and potentially unwanted cell types.

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