Sox17 plays a substantial role in late-stage differentiation of the extraembryonic endoderm in vitro
Sox17 plays a substantial role in late-stage differentiation of the extraembryonic endoderm in vitro
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DOI：
10.1242/jcs.007856
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发表时间：
2007-11-01
影响因子：
4
通讯作者：
Miyazaki, Jun-ichi
中科院分区：
文献类型：
--
作者：
Shimoda, Masafumi;Kanai-Azuma, Masami;Miyazaki, Jun-ichi
Sox 17是一种Sry相关的HMG盒转录因子，在定形内胚层和胚外内胚层（ExE）中发育表达。尽管Sox 17（-/-）小鼠胚胎具有缺陷的定形肠内胚层，但其发育的ExE在形态上是完整的。在这里，我们的目的是调查的作用，Sox 17在ExE的发展，通过使用胚胎干细胞（ESCs）的体外分化系统。虽然强迫Sox 17在胚胎干细胞中的表达并不影响ExE承诺，它促进了胚胎干细胞衍生的原始内胚层细胞分化为内脏和壁内胚层细胞。该事件被Nanog的强制表达抑制，Nanog是ESC分化为ExE的负调节剂。虽然Sox 17（-/-）ESCs可以分化为原始内胚层细胞，但进一步分化严重受损。这些结果表明，Sox 17在体外ExE分化的后期阶段中有实质性的参与。Sox 17（-/-）胚胎干细胞在体外分化过程中，Sox 7的表达受到抑制，但在Sox 17（-/-）胚胎的胚外组织中，Sox 7的表达维持在较高水平。这些发现可能解释了Sox 17（-/-）ESCs和Sox 17（-/-）胚胎的ExE表型之间的差异。
Sox17 is a Sry-related HMG-box transcription factor developmentally expressed in both the definitive endoderm and extraembryonic endoderm (ExE). Although Sox17(-/-) mouse embryos have a defective definitive gut endoderm, their developing ExE is morphologically intact. Here, we aimed to investigate the role of Sox17 in ExE development by using an in vitro differentiation system of embryonic stem cells (ESCs). Although forced Sox17 expression in ESCs did not affect ExE commitment, it facilitated the differentiation of ESC-derived primitive endoderm cells into visceral and parietal endoderm cells. This event was inhibited by the forced expression of Nanog, a negative regulator of differentiation of ESCs into the ExE. Although Sox17(-/-) ESCs could differentiate into primitive endoderm cells, further differentiation was severely impaired. These results indicate a substantial involvement of Sox17 in the late stage of ExE differentiation in vitro. Furthermore, the expression of Sox7 - another Sox factor, concomitantly expressed with Sox17 in the developing ExE - was suppressed during the in vitro differentiation of Sox17(-/-) ESCs, but it was maintained at a high level in the extraembryonic tissues of Sox17(-/-) embryos. These findings possibly explain the discrepancy between the ExE phenotype derived from Sox17(-/-) ESCs and that of Sox17(-/-) embryos.