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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Autores principales:	Eun-Gyung Cho, Jeffrey D Zaremba, Scott R McKercher, Maria Talantova, Shichun Tu, Eliezer Masliah, Shing Fai Chan, Nobuki Nakanishi, Alexey Terskikh, Stuart A Lipton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53ba5c9a0de04197981d40a27e5ed34c
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spelling	oai:doaj.org-article:53ba5c9a0de04197981d40a27e5ed34c2021-11-18T06:47:13ZMEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model.1932-620310.1371/journal.pone.0024027https://doaj.org/article/53ba5c9a0de04197981d40a27e5ed34c2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21901155/?tool=EBIhttps://doaj.org/toc/1932-6203Human 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.Eun-Gyung ChoJeffrey D ZarembaScott R McKercherMaria TalantovaShichun TuEliezer MasliahShing Fai ChanNobuki NakanishiAlexey TerskikhStuart A LiptonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e24027 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eun-Gyung Cho Jeffrey D Zaremba Scott R McKercher Maria Talantova Shichun Tu Eliezer Masliah Shing Fai Chan Nobuki Nakanishi Alexey Terskikh Stuart A Lipton 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.
format	article
author	Eun-Gyung Cho Jeffrey D Zaremba Scott R McKercher Maria Talantova Shichun Tu Eliezer Masliah Shing Fai Chan Nobuki Nakanishi Alexey Terskikh Stuart A Lipton
author_facet	Eun-Gyung Cho Jeffrey D Zaremba Scott R McKercher Maria Talantova Shichun Tu Eliezer Masliah Shing Fai Chan Nobuki Nakanishi Alexey Terskikh Stuart A Lipton
author_sort	Eun-Gyung Cho
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.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/53ba5c9a0de04197981d40a27e5ed34c
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MEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model.

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