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首页> 外文期刊>Cell biology international. >The co-transduction of Nurr1 and Brn4 genes induces the differentiation of neural stem cells into dopaminergic neurons.
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The co-transduction of Nurr1 and Brn4 genes induces the differentiation of neural stem cells into dopaminergic neurons.

机译：Nurr1和Brn4基因的共转导诱导神经干细胞分化为多巴胺能神经元。

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Fetal brain tissue can be used in cell replacement therapy for PD (Parkinson's disease), but there is a poor donor supply of this tissue. NSCs (neural stem cells) may overcome this problem as they can be isolated and expanded in vitro. However, the usage of NSCs is limited because the differentiation of NSCs into specific dopaminergic neurons has proven difficult. In the present study, we investigated the effect of Nurr1 (nuclear receptor related factor 1), a transcription factor specific for the development and maintenance of the midbrain dopaminergic neurons on inducing the differentiation of NSCs into TH (tyrosine hydroxylase) immunoreactive dopaminergic neurons. Nonetheless, these cells exhibited an immature neuronal morphology with small cell bodies and short neurite processes, and they seldom expressed DAT (dopamine transporter), a late marker of mature dopaminergic neurons. However, forced co-expression of Nurr1 with Brn4, a member of the POU domain family of transcription factors, caused immature Nurr1-induced dopaminergic neurons to differentiate into morphologically and phenotypically more mature neurons. Thus the enriched generation of mature dopaminergic neurons by forced expression of Nurr1 with Brn4 may be of future importance in NSC-based cell replacement therapy for PD.
机译：胎儿脑组织可用于PD（帕金森氏病）的细胞替代治疗，但该组织的供体供应不足。 NSC（神经干细胞）可以克服此问题，因为它们可以在体外分离和扩增。但是，NSC的使用受到限制，因为已证明很难将NSC分化为特定的多巴胺能神经元。在本研究中，我们研究了Nurr1（核受体相关因子1）（一种对中脑多巴胺能神经元的发育和维持具有特异性的转录因子）在诱导NSC分化为TH（酪氨酸羟化酶）免疫反应性多巴胺能神经元方面的作用。然而，这些细胞表现出不成熟的神经元形态，具有小的细胞体和短的神经突过程，并且它们很少表达DAT（多巴胺转运蛋白），DAT是成熟的多巴胺能神经元的晚期标志物。但是，Nurr1与Brn4（转录因子POU域家族的成员）的强制共表达导致未成熟的Nurr1诱导的多巴胺能神经元分化为形态和表型更成熟的神经元。因此，通过用Brn4强制表达Nurr1来丰富成熟的多巴胺能神经元的产生，在基于NSC的PD细胞替代治疗中可能具有未来的重要性。

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