miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice
作者单位:Institute of Neurosciences Department of Neurobiology Collaborative Innovation Center for Brain Science School of Basic Medicine Department of Medical Genetics and Developmental Biology Fourth Military Medical University Department of Spinal Surgery Honghui Hospital Xi’an Jiaotong University College of Medicine
会议名称:《中国神经科学学会第十二届全国学术会议》
会议日期:2017年
学科分类:0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词:Neural Stem Cell Neural progenitor Cell miR-342-5p downstreams
摘 要:Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout(Rbp-j c KO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, mi R-342-5 p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the mi R-342-5 p host gene, the Ena-vasodilator stimulated phosphoproteinlike(Evl), was negatively regulated by Notch signaling, probably through HES5. Transfection of mi R-342-5 p promoted the differentiation of neural stem cells(NSCs) into intermediate neural progenitors(INPs) in vitro and reduced the stemness of NSCs in vivo. Furthermore, mi R-342-5 p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that mi R-342-5 p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment.