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

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Neural Stem Cells in Development, Adulthood and Disease

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

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.

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Authors and Affiliations

  1. Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Schillerstrasse 46, 80336, Munich, Germany

    Giacomo Masserdotti

  2. Institute of Stem Cell Research, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany

    Giacomo Masserdotti

  3. Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128, Mainz, Germany

    Benedikt Berninger

  4. Focus Program Translational Neuroscience of the Johannes Gutenberg University Mainz, Mainz, Germany

    Benedikt Berninger

Authors
  1. Giacomo Masserdotti
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  2. Benedikt Berninger
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Correspondence to Benedikt Berninger .

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Editors and Affiliations

  1. Institute for Neuroscience & Physiology University of Gothenburg, Gothenburg, Sweden

    H. Georg Kuhn

  2. Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, USA

    Amelia J. Eisch

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Masserdotti, G., Berninger, B. (2015). Direct Reprogramming of Somatic Cells into Induced Neuronal Cells: Where We Are and Where We Want to Go. In: Kuhn, H., Eisch, A. (eds) Neural Stem Cells in Development, Adulthood and Disease. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1908-6_10

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