Sah D W, Ray J, Gage F H
Signal Pharmaceuticals Incorporated, San Diego, CA 92121, USA.
Nat Biotechnol. 1997 Jun;15(6):574-80. doi: 10.1038/nbt0697-574.
Human central nervous system (CNS) cell lines would substantially facilitate drug discovery and basic research by providing a readily renewable source of human neurons. We isolated clonal human CNS cell lines that had been immortalized with a tetracycline (Tc)-responsive v-myc oncogene; addition of Tc to the growth medium suppressed the oncoprotein rapidly and virtually completely, allowing differentiation to proceed. Two classes of bipotent precursor cells were immortalized: the first class had a default differentiation pathway of neurons only, and the second class had a default differentiation pathway of neurons and astrocytes. We found that after exposure to different external signals in vitro, the environment is capable of redirecting the fate of a particular cell, even in the case of the bipotent precursor cell whose default differentiation pathway was neurons only. These data suggest that extrinsic cues can prevail over intrinsic determinants in directing cell fate in the human CNS.
人类中枢神经系统（CNS）细胞系通过提供易于再生的人类神经元来源，将极大地促进药物研发和基础研究。我们分离出了用四环素（Tc）应答性v-myc癌基因永生化的克隆人类CNS细胞系；向生长培养基中添加Tc可迅速且几乎完全抑制癌蛋白，使分化得以进行。两类双能前体细胞被永生化：第一类细胞的默认分化途径仅为神经元，第二类细胞的默认分化途径为神经元和星形胶质细胞。我们发现，在体外暴露于不同的外部信号后，环境能够重定向特定细胞的命运，即使是默认分化途径仅为神经元的双能前体细胞也是如此。这些数据表明，在指导人类中枢神经系统细胞命运方面，外在信号可以胜过内在决定因素。
