Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene

Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene
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DOI:
10.1073/pnas.93.4.1518
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发表时间:
1996-02-20
影响因子:
11.1
通讯作者:
Gage, FH
Gage, FH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hoshimaru, M;Ray, J;Gage, FH

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一种可调节的逆转录病毒载体,其中的v-myc癌基因是由四环素控制的反式激活因子和人巨细胞病毒最小启动子融合到一个泰特操作序列驱动,用于成年大鼠神经元祖细胞的条件永生化。分离并表征单个克隆HC 2S 2。在加入四环素后Tyro天,HC 2S 2细胞停止增殖,开始延伸神经突,并表达神经元标记物tau、NeuN、神经丝200 kDa和谷氨酸脱羧酶,这与v-myc癌蛋白的产生减少一致,分化的HC 2S 2细胞表达大的钠电流和钙电流,并且可以激发再生动作电位,这些结果表明,v-myc癌基因的抑制可能足以使增殖细胞退出细胞周期,并诱导终末分化。HC 2S 2细胞为研究神经元的分化过程提供了有价值的材料。
A regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to a tet operator sequence was used for conditional immortalization of adult rat neuronal progenitor cells. A single clone, HC2S2, was isolated and characterized, Tyro days after the addition of tetracycline, the HC2S2 cells stopped proliferating, began to extend neurites, and expressed the neuronal markers tau, NeuN, neurofilament 200 kDa, and glutamic acid decarboxylase in accordance with the reduced production of the v-myc oncoprotein, Differentiated HC2S2 cells expressed large sodium and calcium currents and could fire regenerative action potentials, These results suggest that the suppression of the v-myc oncogene may be sufficient to make proliferating cells exit from cell cycles and induce terminal differentiation. The HC2S2 cells will be valuable for studying the differentiation process of neurons.