Efficient Conversion of Human Fibroblasts to Functional Neurons by Sequential Inactivation of PTB/nPTB‐regulated RNA Programs

TL;DRAbstract

Cellular reprogramming can be accomplished by using a set of cell lineage‐specific transcription factors. Our recent work reveals a key RNA program regulated by the RNA binding protein PTB, which is not only necessary but also sufficient to trans‐differentiate diverse cell types into neuronal‐like cells or even functional neurons (Xue et al., Cell 152:82‐96, 2013). In this RNA program, PTB down‐regulation allows the neuronal‐specific microRNA miR124 to more efficiently target its substrates, including multiple components of the REST complex responsible for repressing a large array of neuronal‐specific transcription factors in non‐neuronal cells. Down‐regulated REST also further depresses miR124, thus creating a sustainable signal for reprogrammed cells to maintain the neuronal identity. One application of this new neuronal induction protocol is to convert patient fibroblasts into neurons for mechanistic studies of neurodegenerative diseases. Interesting, unlikely mouse cells, human fib

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