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Chunk #2 — 3. Induced neuronal cells — 3.1. The beginning: induced neuronal cells from developmentally related cells

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Induced neuronal reprogramming.
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The first example of direct conversion to cells of neural lineages using transcription factors is the effort led by Goetz and coworkers [11]. Followed by the observation that Pax6 transduction increased neurogenesis in embryonic cortical precursor cells, they examined whether forced expression of Pax6 in Pax6-negative astrocytes can instruct them to neuronal fate. The authors found that in mere seven days almost half of the Pax6 infected astrocytes were converted into β-tubulin-III-, NeuN-positive neurons, some of which expressed markers for excitatory neurons others for inhibitory neurons. Similarly in a stab wound model, Buffo et al. [12] showed that Olig2 positive cells formed near stab wound lesions can be converted into Dcx+ positive migrating neuroblasts via transduction of a dominant negative form of Olig2 (Olig2-VP16). Olig2-VP16 transduction has been shown to derepress Pax6 which could mechanistically contribute to the instruction of neurogenesis. However, conclusions should be made cautiously when marker expression alone is used as the only criterion to define a neuron. In fact, it was later shown that neurons derived from Pax6, Mash1 and Ngn2 transduced astroglial precursors do not