Overexpression of Nodal promotes differentiation of mouse embryonic stem cells into mesoderm and endoderm at the expense of neuroectoderm formation
Overexpression of Nodal promotes differentiation of mouse embryonic stem cells into mesoderm and endoderm at the expense of neuroectoderm formation
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DOI：
10.1089/scd.2005.14.162
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发表时间：
2005-04-01
影响因子：
4
通讯作者：
Pedersen, RA
中科院分区：
文献类型：
--
作者：
Pfendler, KC;Catuar, CS;Pedersen, RA
了解如何指导胚胎干 (ES) 细胞在分化时的命运对于其最终在治疗应用中的应用至关重要。控制 ES 细胞分化的线索可以在早期胚胎中找到，因为小鼠 ES 细胞在注射到囊胚中后会形成所有三个胚胎胚层的衍生物。影响 ES 细胞分化为胚胎胚层的一种有希望的候选者是转化生长因子-β (TGF-β) 生长因子 Nodal。 Nodal 无效小鼠突变体缺乏中胚层，将 Nodal mRNA 注射到非哺乳动物胚胎中会诱导中胚层和内胚层组织。我们发现，Nodal 在小鼠 ES 细胞中的过度表达不仅导致中胚层和内胚层细胞标记物的上调，而且还导致神经外胚层标记物的下调。这些发现证明了 Nodal 对多能细胞向所有三个初级胚层分化的影响的重要性。因此，改变完整胚胎中负责细胞分化的因子的表达提供了一种在体外将ES细胞命运引导至治疗上有用的细胞类型的方法。
Understanding how to direct the fate of embryonic stem (ES) cells upon differentiation is critical to their eventual use in therapeutic applications. Clues for controlling ES cell differentiation may be found in the early embryo because mouse ES cells form derivatives of all three embryonic germ layers upon injection into blastocysts. One promising candidate for influencing the differentiation of ES cells into the embryonic germ layers is the transforming growth factor-beta (TGF-beta) growth factor, Nodal. Nodal null mouse mutants lack mesoderm, and injection of Nodal mRNA into nonmammalian embryos induces mesodermal and endodermal tissues. We find that overexpression of Nodal in mouse ES cells leads not only to up-regulation of mesodermal and endodermal cell markers but also to down-regulation of neuroectodermal markers. These findings demonstrate the importance of Nodal's influence on the differentiation of pluripotent cells to all three of the primary germ layers. Accordingly, altering expression of factors responsible for cell differentiation in the intact embryo provides an approach for directing ES cell fates in vitro toward therapeutically useful cell types.