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Direct In Vitro Reprogramming of Astrocytes into Induced Neurons

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Neural Reprogramming

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2352))

Abstract

Spontaneous neuronal replacement is almost absent in the postnatal mammalian nervous system. However, several studies have shown that both early postnatal and adult astroglia can be reprogrammed in vitro or in vivo by forced expression of proneural transcription factors, such as Neurogenin-2 or Achaete-scute homolog 1 (Ascl1), to acquire a neuronal fate. The reprogramming process stably induces properties such as distinctly neuronal morphology, expression of neuron-specific proteins, and the gain of mature neuronal functional features. Direct conversion of astroglia into neurons thus possesses potential as a basis for cell-based strategies against neurological diseases. In this chapter, we describe a well-established protocol used for direct reprogramming of postnatal cortical astrocytes into functional neurons in vitro and discuss available tools and approaches to dissect molecular and cell biological mechanisms underlying the reprogramming process.

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Acknowledgments

The following sources of funding from the German Research Foundation (DFG) supported work described in this chapter: CRC1080 (project number 221828878) and CRC1193 (project number 264810226). N.S. received support via a PhD fellowship granted by the Institute of Molecular Biology (IMB), Mainz. F.C. received support from Inneruniversitaere Forschungsfoerderung of the University Medical Center of Johannes Gutenberg University Mainz.

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Authors and Affiliations

  1. Institute of Physiological Chemistry, University Medical Center Johannes Gutenberg University Mainz, Mainz, Germany

    Nesrin Sharif, Filippo Calzolari & Benedikt Berninger

  2. International PhD Programme on Gene Regulation, Epigenetics and Genome Stability, Mainz, Germany

    Nesrin Sharif

  3. Institute of Psychiatry, Psychology, and Neuroscience, Centre for Developmental Neurobiology, King’s College London, London, UK

    Benedikt Berninger

  4. MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK

    Benedikt Berninger

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  1. Nesrin Sharif
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  2. Filippo Calzolari
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Correspondence to Benedikt Berninger .

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  1. Stem Cells, Aging and Neurodegeneration Group, Faculty of Medicine, Department of Clinical Sciences, Neurology, Lund Stem Cell Center, Lund University, Lund, Sweden

    Henrik Ahlenius

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Sharif, N., Calzolari, F., Berninger, B. (2021). Direct In Vitro Reprogramming of Astrocytes into Induced Neurons. In: Ahlenius, H. (eds) Neural Reprogramming. Methods in Molecular Biology, vol 2352. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1601-7_2

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  • DOI: https://doi.org/10.1007/978-1-0716-1601-7_2

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