期刊
FRONTIERS IN NEUROSCIENCE
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2017.00530
关键词
induced neurons; direct neural reprogramming; disease modeling; neurological disorders; neurodegenerative diseases
资金
- New York Stem Cell Foundation
- European Research Council under the European Union [602278]
- ERC Grant [30971]
- Swedish Research Council treatment of the future grant agreement [K2012-99X-22324-01-5]
- Swedish Research Council [70862601/Bagadilico]
- Swedish Parkinson Foundation (Parkinsonfonden)
- Strategic Research Area at Lund University Multipark and StemTherapy
- Swedish Foundation for Strategic Research [FFL12-0074]
- Canadian Institutes of Health Research (CIHR) [358492]
- NIHR Biomedical Research Centre grant
- Swedish Foundation for Strategic Research (SSF) [FFL12-0074] Funding Source: Swedish Foundation for Strategic Research (SSF)
- Medical Research Council [MC_PC_12009] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0616-10011] Funding Source: researchfish
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.
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