Hypoxia-indulcible factors 1α and 2α regulate trophoblast differentiation
Hypoxia-indulcible factors 1α and 2α regulate trophoblast differentiation
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DOI：
10.1128/mcb.25.23.10479-10491.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Simon, MC
中科院分区：
文献类型：
--
作者：
Dahl, KDC;Fryer, BH;Simon, MC
胎盘发育最初发生在低氧（O-2）或缺氧环境中。在本报告中，我们发现两个缺氧诱导因子（HIF α和HIF2 α）在决定小鼠胎盘细胞命运中是必不可少的。HIF是由HIF α和HIF β (ARNT)亚基组成的异源二聚体。来自Arnt（-/-）和Hif2 α(-/-)胚胎的胎盘表现出有缺陷的胎盘血管形成和异常的细胞命运。HIF调控Mash2促进海绵状滋养细胞分化，是滋养细胞巨细胞分化的先决条件。在缺乏Arnt或Hif α的情况下，滋养层干细胞不能产生这些细胞类型，而是变成迷路状滋养层细胞。因此，HIF介导胎盘形态发生、血管生成和细胞命运决定，表明O-2张力是滋养细胞谱系决定的关键调节因子。这种新颖的遗传方法为O-2的作用提供了新的见解，紧张在危及生命的发展；妊娠相关疾病，如先兆子痫。
Placental development initially occurs in a low-oxygen (O-2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF alpha and HIF2 alpha, are essential for determining murine placental cell fates. HIF is a heterodimer composed of HIF alpha and HIF beta (ARNT) subunits. Placentas from Arnt(-/-) and Hif1 alpha(-/-) Hif2 alpha(-/-) embryos exhibit defective placental vascularization and aberrant cell fate adoption. HIF regulation of Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast giant cell differentiation. In the absence of Arnt or Hif alpha, trophoblast stem cells fail to generate these cell types and become labyrinthine trophoblasts instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, and cell fate decisions, demonstrating that O-2, tension is a critical regulator of trophoblast lineage determination. This novel genetic approach provides new insights into the role of O-2, tension in the development of life-threatening; pregnancy-related diseases such as preeclampsia.