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World J Stem Cells. Jul 26, 2019; 11(7): 431-444
Published online Jul 26, 2019. doi: 10.4252/wjsc.v11.i7.431
Using transcription factors for direct reprogramming of neurons in vitro
Layal El Wazan, Daniel Urrutia-Cabrera, Raymond Ching-Bong Wong
Layal El Wazan, Daniel Urrutia-Cabrera, Raymond Ching-Bong Wong, Cellular Reprogramming Unit, Centre for Eye Research Australia, Melbourne 3004, Australia
Layal El Wazan, Daniel Urrutia-Cabrera, Raymond Ching-Bong Wong, Department of Surgery, University of Melbourne, Melbourne 3002, Australia
Raymond Ching-Bong Wong, Ophthalmology, Shenzhen Eye Hospital, Shenzhen 518040, Guangdong Province, China
Author contributions: Wong RCB design the study; El Wazan L, Urrutia-Cabrera D, and Wong RCB wrote the paper.
Supported by funding from the Ophthalmic Research Institute of Australia, the University of Melbourne De Brettville Trust, the Kel and Rosie Day Foundation and the Centre for Eye Research Australia. The Centre for Eye Research Australia receives operational infrastructure support from the Victorian Government.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Raymond Ching-Bong Wong, BSc, PhD, Unit Head, Cellular Reprogramming Unit, Centre for Eye Research Australia, Level 6, 75 Commercial Road, Melbourne 3004, Australia. wongcb@unimelb.edu.au
Telephone: +61-39-9298054
Received: February 22, 2019
Peer-review started: February 24, 2019
First decision: June 5, 2019
Revised: June 7, 2019
Accepted: June 27, 2019
Article in press: June 27, 2019
Published online: July 26, 2019
Abstract

Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries. However, a key challenge is the cellular source for transplantation which is often limited by donor availability. Direct reprogramming provides an exciting avenue to generate specialized neuron subtypes in vitro, which have the potential to be used for autologous transplantation, as well as generation of patient-specific disease models in the lab for drug discovery and testing gene therapy. Here we present a detailed review on transcription factors that promote direct reprogramming of specific neuronal subtypes with particular focus on glutamatergic, GABAergic, dopaminergic, sensory and retinal neurons. We will discuss the developmental role of master transcriptional regulators and specification factors for neuronal subtypes, and summarize their use in promoting direct reprogramming into different neuronal subtypes. Furthermore, we will discuss up-and-coming technologies that advance the cell reprogramming field, including the use of computational prediction of reprogramming factors, opportunity of cellular reprogramming using small chemicals and microRNA, as well as the exciting potential for applying direct reprogramming in vivo as a novel approach to promote neuro-regeneration within the body. Finally, we will highlight the clinical potential of direct reprogramming and discuss the hurdles that need to be overcome for clinical translation.

Keywords: Cell reprogramming, Neuronal subtypes, Transcription factors, Direct reprogramming, Glutamatergic neurons, GABAergic neurons, Retinal neurons

Core tip: Direct reprogramming represents an innovative technology to generate neurons in the lab, which can be used for cell therapy, drug screening and disease modeling for neurodegenerative diseases. In this review we will discuss the current advance in identifying transcription factors to promote direct reprogramming of specialized neuronal subtypes, including glutamatergic, GABAergic, dopaminergic, sensory and retinal neurons. We will also discuss the hurdles that need to be overcome for clinical translation.