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Decoding neural transcriptomes and epigenomes via high-throughput sequencing

Abstract

The mammalian brain is an evolutionary marvel in which engraving and re-engraving of cellular states enable complex information processing and lifelong maintenance. Understanding the mechanisms by which neurons alter and maintain their molecular signatures during information processing is a fundamental goal of neuroscience. Next-generation sequencing (NGS) technology is rapidly transforming the ability to probe the molecular basis of neuronal function. NGS can define not only the complete molecular signatures of cells by transcriptome analyses but also the cascade of events that induce or maintain such signatures by epigenetic analyses. Here we offer some general and practical information to demystify NGS technology and highlight its potential to the neuroscience field. We start with discussion of the complexity of the nervous system, then introduce various applications of NGS with practical considerations and describe basic principles underlying various NGS technologies. Finally, we discuss emerging NGS-related technologies for the neuroscience field.

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Figure 1: Tackling the complexity of the mammalian brain.
Figure 2: Cellular properties that can be determined by today's NGS-powered assays.
Figure 3: Three widely used protocols for strand-specific RNA sequencing library preparation.
Figure 4: Bisulfite sequencing.
Figure 5: Overview of NGS technology using Illumina technology as an example.

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Acknowledgements

We thank K. Christian for comments. The work in the authors' laboratories was supported by the US National Institutes of Health (H.S. and G.-I.M.), the Simons Foundation (SFARI 240011, H.S.) MSCRF (G.-I.M.) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. J.S. was supported by a fellowship from Samsung.

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Shin, J., Ming, Gl. & Song, H. Decoding neural transcriptomes and epigenomes via high-throughput sequencing. Nat Neurosci 17, 1463–1475 (2014). https://doi.org/10.1038/nn.3814

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