MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model

Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apop...

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Main Authors:	Cho, Eun-Gyung, Zaremba, Jeffrey D., McKercher, Scott R., Talantova, Maria, Tu, Shichun, Masliah, Eliezer, Chan, Shing Fai, Nakanishi, Nobuki, Terskikh, Alexey, Lipton, Stuart A.
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162026/

id	pubmed-3162026
recordtype	oai_dc
spelling	pubmed-31620262011-09-07 MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model Cho, Eun-Gyung Zaremba, Jeffrey D. McKercher, Scott R. Talantova, Maria Tu, Shichun Masliah, Eliezer Chan, Shing Fai Nakanishi, Nobuki Terskikh, Alexey Lipton, Stuart A. Research Article Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced expression of constitutively active MEF2C (MEF2CA) generates significantly greater numbers of neurons with dopaminergic properties in vitro. Conversely, RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine—lesioned Parkinsonian rats in vivo, the transplanted cells survive well, differentiate into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a significantly greater degree than non-programmed cells. The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD. Public Library of Science 2011-08-25 /pmc/articles/PMC3162026/ /pubmed/21901155 http://dx.doi.org/10.1371/journal.pone.0024027 Text en Cho et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cho, Eun-Gyung Zaremba, Jeffrey D. McKercher, Scott R. Talantova, Maria Tu, Shichun Masliah, Eliezer Chan, Shing Fai Nakanishi, Nobuki Terskikh, Alexey Lipton, Stuart A.
spellingShingle	Cho, Eun-Gyung Zaremba, Jeffrey D. McKercher, Scott R. Talantova, Maria Tu, Shichun Masliah, Eliezer Chan, Shing Fai Nakanishi, Nobuki Terskikh, Alexey Lipton, Stuart A. MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model
author_facet	Cho, Eun-Gyung Zaremba, Jeffrey D. McKercher, Scott R. Talantova, Maria Tu, Shichun Masliah, Eliezer Chan, Shing Fai Nakanishi, Nobuki Terskikh, Alexey Lipton, Stuart A.
author_sort	Cho, Eun-Gyung
title	MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model
title_short	MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model
title_full	MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model
title_fullStr	MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model
title_full_unstemmed	MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model
title_sort	mef2c enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model
description	Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced expression of constitutively active MEF2C (MEF2CA) generates significantly greater numbers of neurons with dopaminergic properties in vitro. Conversely, RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine—lesioned Parkinsonian rats in vivo, the transplanted cells survive well, differentiate into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a significantly greater degree than non-programmed cells. The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162026/
_version_	1611472581315002368

MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model

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