miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression

	miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression
	Yang, DH; Li, T; Wang, Y; Tang, YJ; Cui, HJ; Tang, Y; Zhang, XJ; Chen, DG; Shen, N; Le, WD
刊名	JOURNAL OF CELL SCIENCE
	2012
卷号	125 期号:7 页码:1673-1682
关键词	Embryonic stem cell MicroRNA miR-132 Nurr1 Dopamine neuron
通讯作者	Le, WD (reprint author), Shanghai Jiao Tong Univ, Chinese Acad Sci, Key Lab Stem Cell Biol, Shanghai Inst Biol Sci,Inst Hlth Sci,Sch Med, 225 S Chongqing Rd, Shanghai 200025, Peoples R China.,weidongl@bcm.edu
英文摘要	Although it is well established that embryonic stem (ES) cells have the potential to differentiate into dopamine neurons, the molecular basis of this process, particularly the role of microRNAs (miRNAs), remains largely unknown. Here we report that miR-132 plays a key role in the differentiation of dopamine neurons by directly regulating the expression of Nurr1 (also known as nuclear receptor subfamily 4 group A member 2; Nr4a2). We constructed a mouse ES cell line CGR8, which stably expresses GFP under the tyrosine hydroxylase (TH) promoter, so the TH-positive neurons could be easily sorted using fluorescence-activated cell sorting (FACS). Then, we performed a miRNA array analysis on the purified TH-positive neurons and found that 45 of 585 miRNAs had more than a fivefold change in expression level during dopamine neuron differentiation. Among the 45 miRNAs, we were particularly interested in miR-132 because this miRNA has been reported to be highly expressed in neurons and to have a potential role in neurodegenerative diseases. We found that the direct downregulation of endogenous miR-132 induced by miR-132 antisense oligonucleotide (miR-132-ASO) promoted the differentiation of TH-positive neurons, whereas ectopic expression of miR-132 in ES cells reduced the number of differentiated TH-positive neurons but did not change the total number of differentiated neurons. Furthermore, we identified that miR-132-ASO could substantially reverse the miR-132-mediated suppression of TH-positive neuron differentiation. Moreover, through a bioinformatics assay we identified the Nurr1 gene as a potential molecular target of miR-132. Using a luciferase-reporter assay and western blot analysis, we demonstrated that miR-132 could directly regulate the expression of Nurr1. Collectively, our data provide the first evidence that miR-132 is an important molecule regulating ES cell differentiation into dopamine neurons by directly targeting Nurr1 gene expression.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	EMBRYONIC STEM-CELLS ; PARKINSONS-DISEASE ; IN-VITRO ; MICRORNA ; MIDBRAIN ; TRANSCRIPTION ; PATHWAY ; BRAIN ; GENE ; TRANSPLANTATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000303911300008
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/626]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yang, DH,Li, T,Wang, Y,et al. miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression[J]. JOURNAL OF CELL SCIENCE,2012,125(7):1673-1682.
APA	Yang, DH.,Li, T.,Wang, Y.,Tang, YJ.,Cui, HJ.,...&Le, WD.(2012).miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression.JOURNAL OF CELL SCIENCE,125(7),1673-1682.
MLA	Yang, DH,et al."miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression".JOURNAL OF CELL SCIENCE 125.7(2012):1673-1682.