Teratocarcinomas and human embryology: Pluripotent human EC cell lines

Teratocarcinomas and human embryology: Pluripotent human EC cell lines
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DOI:
10.1111/j.1699-0463.1998.tb01331.x
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发表时间:
1998-01-01
期刊:
影响因子:
2.8
通讯作者:
Andrews, PW
Andrews, PW
中科院分区:
医学3区
文献类型:
--
作者:
Andrews, PW

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生殖细胞肿瘤(GCT)的组织发生反映了配子发生、受精和随后胚胎细胞分化的正常过程。了解控制胚胎癌 (EC) 细胞分化为各种胚胎和胚胎外细胞类型的机制有助于了解 GCT 的进展。 EC 细胞还提供了一种工具,用于分析胚胎发育过程中控制分化的机制,特别是控制沿替代细胞系 NTERA2 分化为神经元和其他细胞类型以响应视黄酸、HMBA 和骨形态发生蛋白等药物的机制。我们还将多能 NTERA2 EC 细胞与其他人类 EC 细胞系进行了比较,后者的细胞分化能力大大降低。 NTERA2 分化过程中多种基因被激活。特别是,我们发现了 wnt 家族的一个新的人类成员。该 wnt 基因在视黄酸诱导分化后被激活,但随后随着细胞成熟为神经元和其他细胞类型而下调。我们还观察到属于卷曲家族的基因的表达,该家族可能包括编码 wnt 产物受体的基因。因此,在 NTERA2 系统中,与调节胚胎发育期间细胞分化相关的基因被激活,并且似乎在调节这些多能人类 EC 细胞的分化中发挥作用。
The histogenesis of germ cell tumours (GCT) reflects the normal processes of gametogenesis, fertilisation and subsequent embryonic cell differentiation. Understanding the mechanisms that control the differentitation of embryonal carcinoma (EC) cells into a variety of embryonic and extraembryonic cell types is pertinent to understanding the progression of GCT. EC cells also provide a tool for analysing the mechanisms that control differentiation during embryonic development, and particularly the mechanisms that control differentiation along alternative cell line, NTERA2, into neurones and other cell types in response to agents such as retinoic acid, HMBA and the bone morphogenetic proteins. We have also compared the pluripotent NTERA2 EC cells with other human EC cell lines that exhibit a much reduced capacity for cell differentiation. A variety of genes are activated during NTERA2 differentiation. In particular we have identified a novel human member of the wnt family. This,wnt gene is activated following retinoic acid induction of differentiation but is later down-regulated as the cells mature into neurones and other cell types. We have also observed expression of genes belonging to the Frizzled family, which is likely to include genes encoding receptors for the wnt products. Thus in the NTERA2 system, genes pertinent to regulating cell differentiation during embryonic development are activated and appear to play a role in modulating how these pluripotent human EC cells differentiate.