Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?
Frontiers in Neuroscience
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Drouin-Ouellet, J., Pircs, K., Barker, R., Jakobsson, J., & Parmar, M. (2017). Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?. Frontiers in Neuroscience, 11 (530)https://doi.org/10.3389/fnins.2017.00530
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.
direct neural reprogramming, disease modeling, induced neurons, neurodegenerative diseases, neurological disorders
This research has received funding from the New York Stem Cell Foundation, the European Research Council under the European Union's Seventh Framework Programme: FP/2007-2013 Neuro Stem Cell Repair (no. 602278), ERC Grant Agreement no. 30971, the Swedish Research Council treatment of the future grant agreement K2012-99X-22324-01-5, the Swedish Research Council 70862601/Bagadilico, Swedish Parkinson Foundation (Parkinsonfonden), the Strategic Research Area at Lund University Multipark and StemTherapy. JJ is supported by the Swedish Foundation for Strategic Research (#FFL12-0074). JD is supported by a Canadian Institutes of Health Research (CIHR) fellowship (#358492), and RB is supported by an NIHR Biomedical Research Centre grant to the University of Cambridge/Addenbrooke's Hospital. MP is a New York Stem Cell Foundation—Robertson Investigator.
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External DOI: https://doi.org/10.3389/fnins.2017.00530
This record's URL: https://www.repository.cam.ac.uk/handle/1810/274786
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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