Ectopic telomerase expression inhibits neuronal differentiation of NT2 neural progenitor cells.
Ectopic telomerase expression inhibits neuronal differentiation of NT2 neural progenitor cells.
复制标题
异位端粒酶表达抑制 NT2 神经祖细胞的神经元分化。
DOI：
10.1016/j.neulet.2007.03.079
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发表时间：
2007
影响因子：
2.5
通讯作者：
Fillmore,HelenL
中科院分区：
文献类型：
--
作者：
Richardson,RMark;Nguyen,Binh;Holt,ShawnE;Broaddus,WilliamC;Fillmore,HelenL
人们对端粒酶永生化细胞在移植中替代因神经退行性疾病和其他中枢神经系统损伤而丧失的神经元的潜在用途有着极大的兴趣。人端粒酶逆转录酶（human telomerase reverse transcriptase，hTERT）是端粒酶的催化成分，经hTERT基因转导的神经祖细胞（Neural progenitor cells，NPC）具有体外无限增殖和对分化信号应答的潜能，这些分化信号是产生移植所需细胞所必需的。本研究的目的是评估神经元分化的NT 2细胞，一个模型NPC细胞系，后hTERT转导。RT-PCR和端粒酶活性检测结果表明，外源性hTERT持续表达可明显抑制NT 2细胞向神经元的分化。在维甲酸诱导分化后，hTERT-NT 2细胞产生的神经元仅为亲本和载体对照细胞产生的神经元的四分之一。以前在其他hTERT转导的祖细胞系中没有报道过组成型端粒酶活性的分化抑制作用，这意味着端粒酶在具有致瘤潜力的NPC的增殖和分化中具有独特的作用。阐明负责这种效应的机制可能有助于理解端粒酶活性在NPC致瘤性中的潜在作用，以及优化安全的、端粒酶工程化的、可移植的神经元的生产。
There is significant interest in the potential use of telomerase-immortalized cells in transplantation to replace neurons lost to neurodegenerative diseases and other central nervous system injuries. Neural progenitor cells (NPCs) transduced with human telomerase reverse transcriptase (hTERT), the catalytic component of telomerase, have the potential both to proliferate indefinitely in vitro and to respond to differentiation signals necessary for generating appropriate cells for transplantation. The purpose of this study was to evaluate the differentiation of neurons from NT2 cells, a model NPC cell line, following hTERT transduction. RT-PCR and telomerase activity data demonstrated that persistent exogenous hTERT expression significantly inhibited the differentiation of neurons from NT2 cells. Following retinoic acid induced differentiation, hTERT-NT2 cells produced only one fourth of the neurons generated by parental and vector-control cells. A differentiation-inhibiting effect of constitutive telomerase activity has not been reported previously in other hTERT-transduced progenitor cell lines, implying a unique role for telomerase in the proliferation and differentiation of NPCs that have tumorigenic potential. Elucidating the mechanism responsible for this effect may aid in understanding the potential role of telomerase activity in the tumorigenecity of NPCs, as well as in optimizing the production of safe, telomerase-engineered, transplantable neurons.