Bac transgenic embryonic stem cells provide therapy and insights into Parkinson's disease

ESC-derived midbrain dopaminergic (DA) neurons represent a promising tool for applications in Parkinson's disease. However, ESC-based transplantation paradigms carry a risk of introducing inappropriate or tumorigenic cells. Cell purification prior to transplantation may alleviate these concerns and enable the identification of the specific DA neuron stage most suitable for cell therapy.;Here we used three BAC transgenic reporter ESC lines that mark sequential differentiation stages from midbrain precursors to mature DA neurons. While transplantation of purified cells from all three stages resulted in DA neuron engraftment, Nurr1::GFP+ and Pitx3::YFP+ cells yielded functional grafts composed almost exclusively of midbrain DA neurons. Global transcriptome analysis of purified ESC progeny confirmed expression of known and identified novel markers of midbrain DA neuron fate.;These data demonstrate the remarkable fate specificity of in vitro generated ESC-derived DA neurons and the ability to harness defined differentiation stages towards an optimized cell therapy in parkinsonian mice.