miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice.
miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice.
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miR-342-5p 调节小鼠神经干细胞增殖和分化下游的 Notch 信号传导
DOI：
10.1016/j.stemcr.2017.02.017
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发表时间：
2017-04-11
影响因子：
5.9
通讯作者：
Han H
中科院分区：
文献类型：
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作者：
Gao F;Zhang YF;Zhang ZP;Fu LA;Cao XL;Zhang YZ;Guo CJ;Yan XC;Yang QC;Hu YY;Zhao XH;Wang YZ;Wu SX;Ju G;Zheng MH;Han H
Notch信号传导与神经发育密切相关，但其下游效应子仍不完全清楚。在这项研究中，我们培养Nestin-Cre介导的条件性Rbp-j敲除（Rbp-j cKO）和对照胚胎的神经球，并使用微阵列比较它们的miRNA表达谱。在差异表达的miRNA中，miR-342- 5 p显示出上调的表达，因为Notch信号传导被遗传或药物中断。一致地，miR-342- 5 p宿主基因（Ena血管扩张剂刺激的磷蛋白样（Evl））的启动子受到Notch信号传导的负调节，可能是通过HES 5。转染miR-342- 5 p可促进体外培养的神经干细胞（NSCs）向中间神经祖细胞（INPs）分化，并降低体内培养的NSCs的干性。此外，miR-342- 5 p抑制神经干细胞/中间祖细胞向星形胶质细胞的分化，可能通过直接靶向GFAP介导。我们的研究结果表明miR-342- 5 p可以作为Notch信号的下游效应子来调节NSC向INPs的分化和星形胶质细胞的定型。miR-342- 5 p作为经典Notch信号的下游效应物Notch信号通过调节其宿主基因Evl抑制miR-342 - 5 p表达miR-342- 5 p促进NSC向INPs的转变星形胶质细胞定型被靶向GFAP的miR-342- 5 p抑制在这篇文章中，Han和同事表明miR-342- 5 p作为小鼠CNS中Notch信号的下游效应物。Notch信号通过调控宿主基因Evl抑制miR-342- 5 p表达。随着NSCs中Notch信号的减弱，miR-342- 5 p被上调以促进NSCs向INPs的转化，并通过靶向GFAP抑制星形胶质细胞的定型。
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. miR-342-5p acts as a downstream effector of canonical Notch signaling Notch signal inhibits miR-342-5p expression by regulating its host gene Evl miR-342-5p promotes the transition of NSCs into INPs Astrocyte commitment was suppressed by miR-342-5p targeting GFAP In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP.