miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice.
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 cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs) into intermediate neural progenitors (INPs) in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment.
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China; Institute of Neurosciences, Department of Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Fang
F
Gao
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Yu-Fei
YF
Zhang
Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
Zheng-Ping
ZP
Zhang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Luo-An
LA
Fu
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Xiu-Li
XL
Cao
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Yi-Zhe
YZ
Zhang
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Chen-Jun
CJ
Guo
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Xian-Chun
XC
Yan
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China; Institute of Neurosciences, Department of Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Qin-Chuan
QC
Yang
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Yi-Yang
YY
Hu
Institute of Neurosciences, Department of Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Xiang-Hui
XH
Zhao
Institute of Neurosciences, Department of Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Ya-Zhou
YZ
Wang
Institute of Neurosciences, Department of Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
Sheng-Xi
SX
Wu
Institute of Neurosciences, Department of Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China. Electronic address: jugong@fmmu.edu.cn.
Gong
G
Ju
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China. Electronic address: minhua_zheng@126.com.
Min-Hua
MH
Zheng
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China. Electronic address: huahan@fmmu.edu.cn.
Hua
H
Han
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D005904:Glial Fibrillary Acidic Protein; D035683:MicroRNAs; C581863:Mirn342 microRNA, mouse; D051880:Receptors, Notch; C528900:glial fibrillary astrocytic protein, mouse
Notch; RBP-J; glia; intermediate neural progenitors; miR-342-5p; neural stem cells; neuron