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Chunk #11 — 3. Induced neuronal cells — 3.2. Crossing major lineage boundaries: mesodermal to ectodermal conversion

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Induced neuronal reprogramming.
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and dopamine HPLC measurements. The same transcription factor combination was shown to also convert human fetal and adult fibroblasts into iDaN cells albeit with a much lower efficiency. Similar to mouse iDaN cells, human induced dopaminergic neurons are also positive for multiple dopaminergic neuronal markers (VMAT2, DAT and ALDH1A1), actively spiking and released dopamine. Despite the higher purity of TH positive neurons (reported fractions of 85% and 60% in mouse and human fetal fibroblasts, respectively), there are still clear differences between the gene expression profile of iDaN cells and that of bona fide midbrain dopaminergic neurons. Encouraging of course was the observation that the overall transcriptome of induced cells were more similar to dopamine neurons than to fibroblasts. Importantly, cell transplantation experiments were conducted into neonatal mouse brains and it was shown that the ANL transduced iDaN cells could functionally integrate into the mouse brain. The cells were not yet tested though for the ability to restore dopamine deficiency in vivo in animal models for Parkinson’s disease. To address this question, Kim and colleagues subsequently used tail tip fibroblasts from Pitx3-GFP knock-in mice and screened for factors that induce GFP expression[32]. Pitx3 is a member of the RIEG/PITX homeobox family