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

JC Niclis; CW Gantner; CPJ Hunt; JA Kauhausen; JC Durnall; JM Haynes; CW Pouton; CL Parish; LH Thompson

Journal article

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

JC Niclis, CW Gantner, CPJ Hunt, JA Kauhausen, JC Durnall, JM Haynes, CW Pouton, CL Parish, LH Thompson

Stem Cell Reports | CELL PRESS | Published : 2017

DOI: 10.1016/j.stemcr.2017.08.002

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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 ..

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University of Melbourne Researchers

Cameron Hunt Author

Clare Parish Author

Lachlan Thompson Author

Related Projects (1)

STANDARDISING PROTOCOLS FOR THE DIFFERENTIATION AND INTEGRATION OF HUMAN PLURIPOTENT STEM CELL-DERIVED NEURAL TRANSPLANTS IN PARKINSON'S DISEASE

Clinical trials have shown that transplanting dopamine neurons (specific nerve cells) into the brain of Parkinson’s disease patients can imp..

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Awarded by Institute of Neurosciences, Mental Health and Addiction

Funding Acknowledgements

The authors thank Mong Tien for expert technical assistance. C.P. is a Viertel Senior Research Fellow. This work was supported NHMRC project grants #1042584 and #1102704. The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.