BMP4 initiates human embryonic stem cell differentiation to trophoblast
BMP4 initiates human embryonic stem cell differentiation to trophoblast
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DOI：
10.1038/nbt761
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发表时间：
2002-12-01
影响因子：
46.9
通讯作者：
Thomson, JA
中科院分区：
文献类型：
--
作者：
Xu, RH;Chen, X;Thomson, JA
人类胚胎干细胞（ES）（1,2）在移植治疗中潜在作用所引发的兴奋与争议，常常掩盖了其作为一种用于理解人类组织发育和功能的基础研究工具的可能更为重要的用途。人类ES细胞可以无限增殖，并能形成所有三个胚胎胚层的高级衍生物。但较少被广泛认识到的是，人类ES细胞还能形成在原肠胚形成之前从胚胎分化出来的胚外组织。利用人类ES细胞来获取早期人类滋养层细胞尤其有价值，因为它很难从其他来源获得，且与小鼠滋养层细胞有显著差异。在此我们表明，骨形态发生蛋白4（BMP4），转化生长因子 -β（TGF -β）超家族的一个成员，能诱导人类ES细胞向滋养层细胞分化。DNA微阵列、逆转录聚合酶链反应（RT - PCR）和免疫测定分析表明，分化的细胞表达一系列滋养层细胞标志物并分泌胎盘激素。当以低密度接种时，经BMP4处理的细胞形成表达绒毛膜促性腺激素（CG）的合胞体。这些结果凸显了人类和小鼠ES细胞之间的根本差异，小鼠ES细胞即使能向滋养层细胞分化，其分化能力也很差（3）。因此，人类ES细胞为研究早期人类滋养层细胞的分化和功能提供了一个工具，并可能为人类着床后发育的一些最早的分化事件提供新的认识。
The excitement and controversy surrounding the potential role of human embryonic stem (ES)(1,2) cells in transplantation therapy have often overshadowed their potentially more important use as a basic research tool for understanding the development and function of human tissues. Human ES cells can proliferate without a known limit and can form advanced derivatives of all three embryonic germ layers. What is less widely appreciated is that human ES cells can also form the extra-embryonic tissues that differentiate from the embryo before gastrulation. The use of human ES cells to derive early human trophoblast is particularly valuable, because it is difficult to obtain from other sources and is significantly different from mouse trophoblast. Here we show that bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor-beta (TGF-beta) superfamily, induces the differentiation of human ES cells to trophoblast. DNA microarray, RT-PCR, and immunoassay analyses demonstrate that the differentiated cells express a range of trophoblast markers and secrete placental hormones. When plated at low density, the BMP4-treated cells form syncytia that express chorionic gonadotrophin (CG). These results underscore fundamental differences between human and mouse ES cells, which differentiate poorly, if at all, to trophoblast(3). Human ES cells thus provide a tool for studying the differentiation and function of early human trophoblast and could provide a new understanding of some of the earliest differentiation events of human postimplantation development.