Regulation of Neural Stem Cell Differentiation by Transcription Factors HNF4-1 and MAZ-1
Regulation of Neural Stem Cell Differentiation by Transcription Factors HNF4-1 and MAZ-1
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转录因子 HNF4-1 和 MAZ-1 对神经干细胞分化的调节
DOI：
10.1007/s12035-012-8335-0
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发表时间：
2013-02
影响因子：
5.1
通讯作者：
Wen, Tieqiao
中科院分区：
文献类型：
--
作者：
Wang, Jiao;Cheng, Hua;Li, Xiao;Lu, Wei;Wang, Kai;Wen, Tieqiao
神经干细胞（Neural Stem Cells，NSCs）具有分化为神经元、星形胶质细胞和少突胶质细胞的能力，是治疗多种神经系统疾病的理想候选细胞。在此过程中，Rho GTP酶通过下游效应物对细胞骨架产生影响，从而在神经突发生、轴突形成和树突发育中发挥重要作用。Rho GTP酶的活性由Rho-GDP解离抑制剂（Rho-GDI）控制。如我们以前的研究所示，这些也参与了神经干细胞的分化;然而，对潜在的调控机制知之甚少。在此，我们描述了转录因子肝核因子（HNF 4 -1）和myc相关锌指蛋白（MAZ-1）在刺激NSC分化中如何调节Rho-GDIγ的表达。使用转染的顺式元件的双链寡脱氧核苷酸（ODNs）的策略，被称为“诱饵”ODNs，我们研究了HNF 4 -1和MAZ-1对NSC分化的影响在NSC线C17.2。我们的研究结果表明HNF 4 -1和MAZ-1诱骗ODNs显著地敲低Rho-GDIγ基因的转录，导致NSC向神经元分化。我们观察到HNF-4 -1和MAZ-1诱骗ODN能够进入细胞核并与其靶转录因子特异性结合。此外，Rho-GDIγ介导的基因表达也得到了证实，提示转录因子MAZ-1和HNF 4 -1是神经干细胞分化的调控机制。这些结果表明HNF 4 -1和MAZ-1调节Rho-GDIγ的表达并有助于NSCs的分化。我们的研究结果为神经干细胞分化过程中的调控机制研究提供了新的视角，特别是转录因子诱饵在体内的临床应用，为神经退行性疾病的治疗提供了潜在的策略。
Neural stem cells (NSCs) are promising candidates for a variety of neurological diseases due to their ability to differentiate into neurons, astrocytes, and oligodentrocytes. During this process, Rho GTPases are heavily involved in neuritogenesis, axon formation and dendritic development, due to their effects on the cytoskeleton through downstream effectors. The activities of Rho GTPases are controlled by Rho-GDP dissociation inhibitors (Rho-GDIs). As shown in our previous study, these are also involved in the differentiation of NSCs; however, little is known about the underlying regulatory mechanism. Here, we describe how the transcription factors hepatic nuclear factor (HNF4-1) and myc-associated zinc finger protein (MAZ-1) regulate the expression of Rho-GDIγ in the stimulation of NSC differentiation. Using a transfection ofcis-element double-stranded oligodeoxynucleotides (ODNs) strategy, referred to as “decoy” ODNs, we examined the effects of HNF4-1 and MAZ-1 on NSC differentiation in the NSC line C17.2. Our results show that HNF4-1 and MAZ-1 decoy ODNs significantly knock down Rho-GDIγ gene transcription, leading to NSC differentiation towards neurons. We observed that HNF4-1 and MAZ-1 decoy ODNs are able enter to the cell nucleolus and specifically bind to their target transcription factors. Furthermore, the expression of Rho-GDIγ-mediated genes was identified, suggesting that the regulatory mechanism for the differentiation of NSCs is triggered by the transcription factors MAZ-1 and HNF4-1. These findings indicate that HNF4-1 and MAZ-1 regulate the expression of Rho-GDIγ and contribute to the differentiation of NSCs. Our findings provide a new perspective within regulatory mechanism research during differentiation of NSCs, especially the clinical application of transcription factor decoys in vivo, suggesting potential therapeutic strategies for neurodegenerative disease.
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肠上皮细胞中HNF4Alpha靶基因的映射。
影响因子：
2.4
作者：
Boyd M;Bressendorff S;Møller J;Olsen J;Troelsen JT
通讯作者：
Troelsen JT
DOI：
10.1159/0000109603
发表时间：
2007
期刊：
Endocrine development
影响因子：
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作者：
M. Maestro;C. Cardalda;S. Boj;R. F. Luco;J. Servitja;J. Ferrer
通讯作者：
M. Maestro;C. Cardalda;S. Boj;R. F. Luco;J. Servitja;J. Ferrer
影响因子：
4.6
作者：
Burns TC;Steinberg GK
通讯作者：
Steinberg GK
bFGF、肝素和层粘连蛋白的组合在体外和体内诱导大鼠神经干细胞产生多巴胺能神经元
影响因子：
4.4
作者：
Yu, Yiqun;Gu, Shuting;Wen, Tieqiao
通讯作者：
Wen, Tieqiao
DOI：
10.1007/978-94-015-9460-8_17
发表时间：
2000
期刊：
--
影响因子：
--
作者：
Hai Li;Zhenbiao Yang
通讯作者：
Hai Li;Zhenbiao Yang