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Front Neurosci. 2017 Sep 28;11:530. doi: 10.3389/fnins.2017.00530. eCollection 2017.

Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?

Author information

1
Department of Experimental Medical Science, Division of Neurobiology and Lund Stem Cell Center, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
2
John van Geest Centre for Brain Repair and Department of Neurology, Department of Clinical Neurosciences and Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.

Abstract

Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs) is the potential to maintain aging and epigenetic signatures of the donor, which is critical given that many diseases of the CNS are age related. Here, we review the published literature on the work that has been undertaken using iNs to model human brain disorders. Furthermore, as disease-modeling studies using this direct neuronal reprogramming approach are becoming more widely adopted, it is important to assess the criteria that are used to characterize the iNs, especially in relation to the extent to which they are mature adult neurons. In particular: i) what constitutes an iN cell, ii) which stages of conversion offer the earliest/optimal time to assess features that are specific to neurons and/or a disorder and iii) whether generating subtype-specific iNs is critical to the disease-related features that iNs express. Finally, we discuss the range of potential biomedical applications that can be explored using patient-specific models of neurological disorders with iNs, and the challenges that will need to be overcome in order to realize these applications.

KEYWORDS:

direct neural reprogramming; disease modeling; induced neurons; neurodegenerative diseases; neurological disorders

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