SIRT1 suppresses self-renewal of adult hippocampal neural stem cells

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	SIRT1 suppresses self-renewal of adult hippocampal neural stem cells
	Ma, Chen-yan; Yao, Mao-jin; Zhai, Qi-wei; Jiao, Jian-wei; Yuan, Xiao-bing; Poo, Mu-ming
刊名	DEVELOPMENT
	2014
卷号	141 期号:24 页码:4697-4709
关键词	CENTRAL-NERVOUS-SYSTEM CALORIE RESTRICTION TRANSCRIPTION FACTORS DEPENDENT REGULATION MAMMALIAN SIRTUINS GENE-EXPRESSION LIFE-SPAN NEUROGENESIS DEACETYLASE DIFFERENTIATION
通讯作者	Ma, CY (reprint author), Chinese Acad Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
英文摘要	The balance between self-renewal and differentiation of adult neural stem cells (aNSCs) is essential for the maintenance of the aNSC reservoir and the continuous supply of new neurons, but how this balance is fine-tuned in the adult brain is not fully understood. Here, we investigate the role of SIRT1, an important metabolic sensor and epigenetic repressor, in regulating adult hippocampal neurogenesis in mice. We found that there was an increase in SIRT1 expression during aNSC differentiation. In Sirt1 knockout (KO) mice, as well as in brain-specific and inducible stem cell-specific conditional KO mice, the proliferation and self-renewal rates of aNSCs in vivo were elevated. Proliferation and self-renewal rates of aNSCs and adult neural progenitor cells (aNPCs) were also elevated in neurospheres derived from Sirt1 KO mice and were suppressed by the SIRT1 agonist resveratrol in neurospheres from wild-type mice. In cultured neurospheres, 2-deoxy-D-glucose-induced metabolic stress suppressed aNSC/aNPC proliferation, and this effect was mediated in part by elevating SIRT1 activity. Microarray and biochemical analysis of neurospheres suggested an inhibitory effect of SIRT1 on Notch signaling in aNSCs/aNPCs. Inhibition of Notch signaling by a gamma-secretase inhibitor also largely abolished the increased aNSC/aNPC proliferation caused by Sirt1 deletion. Together, these findings indicate that SIRT1 is an important regulator of aNSC/aNPC self-renewal and a potential mediator of the effect of metabolic changes.
学科主题	Developmental Biology
WOS标题词	Developmental Biology
语种	英语
WOS记录号	WOS:000346431900006
公开日期	2015-05-27
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/2679]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Ma, Chen-yan,Yao, Mao-jin,Zhai, Qi-wei,et al. SIRT1 suppresses self-renewal of adult hippocampal neural stem cells[J]. DEVELOPMENT,2014,141(24):4697-4709.
APA	Ma, Chen-yan,Yao, Mao-jin,Zhai, Qi-wei,Jiao, Jian-wei,Yuan, Xiao-bing,&Poo, Mu-ming.(2014).SIRT1 suppresses self-renewal of adult hippocampal neural stem cells.DEVELOPMENT,141(24),4697-4709.
MLA	Ma, Chen-yan,et al."SIRT1 suppresses self-renewal of adult hippocampal neural stem cells".DEVELOPMENT 141.24(2014):4697-4709.