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学科主题: 临床医学
题名:
Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells
作者: 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
发表日期: 2011-01-14
DOI: 10.1016/j.bbrc.2010.12.014
卷: 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
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
项目资助者: National Natural Sciences Foundation of China ; Beijing Natural Science Foundation
WOS记录号: WOS:000286543800006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62109
Appears in Collections:北京大学第三临床医学院_神经内科_期刊论文

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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

Recommended Citation:
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.
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