ID gene expression varies with lineage during differentiation of pluripotential male germ cell tumor cell lines
ID gene expression varies with lineage during differentiation of pluripotential male germ cell tumor cell lines
复制标题
多能雄性生殖细胞肿瘤细胞系分化过程中ID基因表达随谱系变化
DOI：
10.1007/s004410000340
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发表时间：
2001
影响因子：
3.6
通讯作者：
R. Chaganti
中科院分区：
文献类型：
--
作者：
J. Houldsworth;V. Reuter;G. Bosl;R. Chaganti
人类男性生殖细胞肿瘤（GCT）是一个很好的模型系统，用于了解控制细胞分化和谱系决定的分子事件。来源于GCT的多潜能胚胎癌细胞系可被诱导，以根据分化剂沿着沿着特定谱系进行终末分化。我们在这里报告，一个这样的细胞系，NTera 2/克隆D1（NT 2/D1），以前显示经历分化沿着神经元谱系的全反式维甲酸（RA），可以诱导沿着一个独特的非神经元谱系的哺乳动物形态发生蛋白，骨形态发生蛋白-2和-4（BMP-2和-4）。关于控制这种人类血统决定的分子事件，我们知之甚少。在这项研究中，作为抑制剂的螺旋-环-螺旋（HLH）转录激活因子参与谱系承诺的功能的ID（分化和DNA结合抑制剂）家族的基因的作用进行了研究，使用两个多能GCT细胞系作为模型系统。在研究的分化程序中，注意到Id 1下降，这一事件通常与分化期间发生的增殖率下降有关。然而，ID 2和ID 3家族成员的表达在程序之间检测到差异。值得注意的是，在RA诱导的NT 2/D1细胞分化期间观察到Id 3的增加，而在NT 2/D1细胞的BMP-2和BMP-4处理期间以及在细胞系27 X-1中诱导内胚层样分化程序期间，Id 2水平增加。多能雄性GCT细胞系包含一个独特的系统，其中可以研究特定基因如ID基因家族在人类细胞分化和谱系决定中的作用。
Human male germ cell tumors (GCTs) comprise an excellent model system for understanding the molecular events controlling cellular differentiation and lineage decision. Pluripotential embryonal carcinoma cell lines derived from GCTs can be induced to undergo terminal differentiation along specific lineages dependent upon the differentiating agent. We report here that one such cell line, NTera2/clone D1 (NT2/D1), previously shown to undergo differentiation along a neuronal lineage by all-trans-retinoic acid (RA), can be induced along a distinct non-neuronal lineage by the mammalian morphogens, bone morphogenetic proteins-2 and -4 (BMP-2 and -4). Very little is known regarding the molecular events that govern such human lineage decisions. In this study, the role of theID(inhibitor of differentiation and DNA-binding) family of genes that act as inhibitors of the function of helix-loop-helix (HLH) transcriptional activators involved in lineage commitment was investigated using two pluripotential GCT cell lines as a model system. In the differentiation programs studied, Id1 was noted to decline, an event often associated with the decrease in proliferative rate occurring during differentiation. However, differences in the expression ofID2 andID3 family members were detected between the programs. Notably, an increase in Id3 during RA-induced differentiation of NT2/D1 cells was observed, while Id2 levels increased during BMP-2 and -4 treatment of NT2/D1 cells and during the induction of an endodermal-like differentiation program in the cell line, 27X-1. The pluripotential male GCT cell lines comprise a unique system in which the roles of specific genes such as theIDfamily of genes in human cell differentiation and lineage decision can be studied.