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Chunk #25 — Induction of Specific Subtypes of Mouse and Human iN cells

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Induced neuronal cells: how to make and define a neuron.
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and culture conditions, colonies appeared that closely resembled neural rosette cells and expressed several relevant markers. Upon spontaneous differentiation, these iNPCs could give rise to multiple neuronal subtypes and astrocytic cells, indicating that the iNPCs were at least bi-potential neural precursor cells, but cells with oligodendrocytic characteristics were not seen; notably, a very similar approach was also used to generate cardiomyocytes and blood progenitor cells from fibroblasts (Szabo et al., 2010; Efe et al., 2011). In these studies, the authors claimed that the observed transdifferentiation bypassed an intermediate pluripotent stage because no Oct4 transcripts were observed in the cell population and the short reprogramming factor expression was not compatible with iPS cell generation. However, as the same approach can generate multiple somatic as well as pluripotent lineages, the simplest explanation is that short-term expression of the pluripotency reprogramming factors indeed induces a transient pluripotent state, but this state is unstable and prone to differentiation, and cannot be stabilized by environmental cues only (Figure 2). Future studies will address whether a “direct” conversion between fibroblasts and neural progenitors is possible using neural transcription factors (Figure 2). Although this approach is intriguing, the efficiency of forming rosette-like colonies appeared low and the