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Chunk #4 — Direct conversion of mouse fibroblasts to neurons

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Induced neuronal cells: how to make and define a neuron.
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This first iN cell study raised many new questions that the field has now begun to address. Among other things, it was unclear what the exact cell of origin for iN cells was and whether endodermal cells could be coaxed towards iN cells. From a developmental point of view, it remained unresolved whether the reprogramming involved an intermediate neural progenitor cell, how similar iN cells are compared to bona fide neurons, whether iN cells possessed a regional identity and if modifying the combination of transcription factors would bestow a specific neural subtype identity. Chromatin biologists would be interested to know how complete the epigenetic landscape is remodeled towards a neuronal pattern and whether the reprogramming factors initiate the neurogenic program while suppressing the original cell fates or iN cells retain molecular "memories" of their cell of origin. Important for potential translational aspects the questions remained whether iN cells can functionally integrate into the brain and last but not least whether methods could be developed to generate human iN cells. In the past few months a number of reports have been published that provide the first answers to some of these questions and we will discuss those in the following sections.