Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during Embryonic Stem Cell Neural Differentiation.

Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during Embryonic Stem Cell Neural Differentiation.
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Mir-29b 介导胚胎干细胞神经分化过程中神经管与神经嵴的命运决定

DOI:
10.1016/j.stemcr.2017.06.017
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发表时间:
2017-08-08
期刊:
影响因子:
5.9
通讯作者:
Kang J
Kang J
中科院分区:
医学1区
文献类型:
--
作者:
Xi J;Wu Y;Li G;Ma L;Feng K;Guo X;Jia W;Wang G;Yang G;Li P;Kang J

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在原肠胚形成期间,神经外胚层细胞形成神经管和神经嵴。神经系统比其他组织含有更多的microRNA,但microRNA在控制神经外胚层细胞分化为神经管上皮(NTE)细胞和神经嵴细胞(NCC)中的作用仍然未知。使用胚胎干细胞(ESC)神经分化系统,我们发现miR-29 b在NTE细胞中上调,在NCC中下调。miR-29 b促进ESCs向NTE细胞分化,并抑制其向NCC分化。因此,抑制miR-29 b显著抑制了NTE细胞的分化。一项机制研究表明,miR-29 b靶向DNA甲基转移酶3a(Dnmt 3a)调节神经分化。此外,miR-29 b介导了Pou 3f 1的功能,Pou 3f 1是一种关键的神经转录因子。因此,我们的研究表明,Pou 3f 1-miR-29 b-Dnmt 3a调节轴在神经分化的初始阶段是活跃的,并调节细胞命运的决定。MiR-29 b促进NTE分化并抑制ESCs向NCC分化MiR-29 b靶向Dnmt 3a调节神经分化MiR-29 b介导Pou 3f 1的功能Pou 3f 1-miR-29 b-Dnmt 3a轴调节细胞命运决定Kang和同事证明了miR-29 b介导了一个关键的神经转录因子Pou 3f 1的功能,以促进ESCs向NTE细胞的分化,并通过靶向Dnmt 3a抑制其向NCC的分化。这项研究表明,Pou 3f 1-miR-29 b-Dnmt 3a调节轴在神经分化的初始阶段是活跃的,并调节细胞命运决定。
During gastrulation, the neuroectoderm cells form the neural tube and neural crest. The nervous system contains significantly more microRNAs than other tissues, but the role of microRNAs in controlling the differentiation of neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural differentiation systems, we found that miR-29b was upregulated in NTE cells and downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE cells and inhibited their differentiation into NCCs. Accordingly, the inhibition of miR-29b significantly inhibited the differentiation of NTE cells. A mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a) to regulate neural differentiation. Moreover, miR-29b mediated the function of Pou3f1, a critical neural transcription factor. Therefore, our study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated the determination of cell fate. MiR-29b promoted NTE differentiation and inhibited NCC differentiation from ESCs MiR-29b targeted Dnmt3a to regulate neural differentiation MiR-29b mediated the function of Pou3f1 The Pou3f1-miR-29b-Dnmt3a axis regulated the cell fate determination In this article, Kang and colleagues demonstrated that miR-29b mediated the function of a critical neural transcription factor Pou3f1 to promote the differentiation of ESCs into NTE cells and inhibit their differentiation into NCCs by targeting Dnmt3a. This study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated cell fate determination.
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