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Chunk #9 — 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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In addition to inhibitory neurons there are several other clinically relevant neuronal subtypes which are the focus of intense investigation. One of those cell types are dopamine neurons of the ventral midbrain type. Given the cell type’s importance a large body of literature has characterized the molecular pathways and transcription factors involved in specifying the dopaminergic lineage [29]. Pfisterer and coworkers combined several dopamine-specific transcription factors with the BAM factors and found that the addition of Lmx1a and FoxA2 is sufficient to generate induced dopaminergic neuronal (iDaN) cells from human fetal fibroblasts[30]. Those iDaN cells are tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) positive, the two enzymes critical for dopamine synthesis. Those iDaN cells also exhibit spontaneous and pacemaking like action potential unique to dopaminergic neurons. These findings were exciting and promising because they demonstrated the principle that methods can be designed to induce iN cells of specific neuronal subtypes. However, some bottlenecks remained such as (a) only up to 25% of the total iN cells were TH positive and the culture remained rather heterogeneous, (b) it is