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学科主题临床医学
Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells
Zhang, Yun1,2; Wang, Jing1,2; Chen, Guian2,3; Fan, Dongsheng1,2; Deng, Min1,2
关键词Sirt1 Human embryonic stem cell Motoneuron differentiation Motoneuron disease
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2011-01-14
DOI10.1016/j.bbrc.2010.12.014
404期:2页:610-614
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
资助者National Natural Sciences Foundation of China ; Beijing Natural Science Foundation ; National Natural Sciences Foundation of China ; Beijing Natural Science Foundation
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]DIRECTED DIFFERENTIATION ; MOTOR-NEURONS ; NICOTINAMIDE INHIBITION ; SPECIFICATION ; NEUROGENIN2 ; IDENTITY ; GENES ; ROLES ; OLIG2 ; MICE
英文摘要

Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and beta III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 mu M) or inhibitor nicotinamide (100 mu M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease. (C) 2010 Elsevier Inc. All rights reserved.

语种英语
所属项目编号30740049 ; 30700906 ; 30700239 ; 30871359 ; 7082099
资助者National Natural Sciences Foundation of China ; Beijing Natural Science Foundation ; National Natural Sciences Foundation of China ; Beijing Natural Science Foundation
WOS记录号WOS:000286543800006
引用统计
被引频次:32[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62109
专题北京大学第三临床医学院_神经内科
作者单位1.Peking Univ Third Hosp, Dept Neurol, Beijing 100191, Peoples R China
2.Peking Univ Third Hosp, Clin Stem Cell Ctr, Beijing 100191, Peoples R China
3.Peking Univ Third Hosp, Reprod Med Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Yun,Wang, Jing,Chen, Guian,et al. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2011,404(2):610-614.
APA Zhang, Yun,Wang, Jing,Chen, Guian,Fan, Dongsheng,&Deng, Min.(2011).Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,404(2),610-614.
MLA Zhang, Yun,et al."Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 404.2(2011):610-614.
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