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Direct neuronal reprogramming for disease modeling studies using patient-derived neurons : What have we learned?

Drouin-Ouellet, Janelle LU ; Pircs, Karolina LU orcid ; Barker, Roger A. LU ; Jakobsson, Johan LU orcid and Parmar, Malin LU orcid (2017) In Frontiers in Neuroscience 11(SEP).
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... (More)

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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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Direct neural reprogramming, Disease modeling, Induced neurons, Neurodegenerative diseases, Neurological disorders
in
Frontiers in Neuroscience
volume
11
issue
SEP
article number
530
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85043774199
  • pmid:29033781
ISSN
1662-4548
DOI
10.3389/fnins.2017.00530
language
English
LU publication?
yes
id
1aefc016-7934-4ab2-b99a-04213fd2339d
date added to LUP
2018-03-28 07:01:29
date last changed
2024-06-25 14:49:16
@article{1aefc016-7934-4ab2-b99a-04213fd2339d,
  abstract     = {{<p>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.</p>}},
  author       = {{Drouin-Ouellet, Janelle and Pircs, Karolina and Barker, Roger A. and Jakobsson, Johan and Parmar, Malin}},
  issn         = {{1662-4548}},
  keywords     = {{Direct neural reprogramming; Disease modeling; Induced neurons; Neurodegenerative diseases; Neurological disorders}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{SEP}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Neuroscience}},
  title        = {{Direct neuronal reprogramming for disease modeling studies using patient-derived neurons : What have we learned?}},
  url          = {{http://dx.doi.org/10.3389/fnins.2017.00530}},
  doi          = {{10.3389/fnins.2017.00530}},
  volume       = {{11}},
  year         = {{2017}},
}