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RESEARCH PRODUCT

Direct Reprogramming of Somatic Cells into Induced Neuronal Cells: Where We Are and Where We Want to Go

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Direct reprogramming of somatic cells has emerged as a novel strategy to generate neurons, including those of human origin. The method provides enormous potential for studying the mechanisms directing neuronal differentiation, the modeling of neurodegenerative diseases, and the development of potential novel approaches for brain repair. In this chapter, we briefly trace the history of reprogramming, as well as the strategies employed to date for converting different types of somatic cells, including fibroblasts, hepatocytes, astrocytes, and pericytes into induced neuronal cells of different subtype identity. Reprogramming involves particular emphasis on transcriptional and posttranscriptional mechanisms, which include an arsenal of transcription factors, including among others the pro-neural genes Ascl1 and Neurog2, noncoding RNAs such as miRNA 124 and miRNA 9/9*, and epigenetic modifiers such as the brahma-associated factors (BAF) complex summarized in Fig. 1. Finally, we discuss upcoming challenges to further improve this technology and the promises it holds for our understanding and treatment of currently incurable diseases.