HOP/NECC1, a novel regulator of mouse trophoblast differentiation
HOP/NECC1, a novel regulator of mouse trophoblast differentiation
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DOI：
10.1074/jbc.m701380200
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发表时间：
2007-08-17
影响因子：
4.8
通讯作者：
Wake, Norio
中科院分区：
文献类型：
--
作者：
Asanoma, Kazuo;Kato, Hidenori;Wake, Norio
同源结构域蛋白(HOP/NECC1)是新近发现的一种调节心脏特异基因表达的基因，在绒毛膜癌克隆1中不表达。最近，有报道称HOP/NECC1抑制了绒毛膜癌的发生。在这里，我们研究了野生型小鼠胎盘中HOP/NECC1的时间表达谱。我们发现E8.5-E9.5野生型胎盘在巨细胞层和海绵滋养层表达HOP/NECC1。HOP/NECC1(-/-)胎盘表现出明显的巨细胞层增殖，进而减少海绵状滋养层细胞的形成。我们证明了SRF在分化中的滋养层细胞中转录活性增加，并且在滋养层干细胞(TS)细胞系中强制表达SRF可以诱导其分化为巨细胞。HOP/NECC1蛋白结合对血清反应因子(SRF)的负调节作用至少部分导致了这些胎盘缺陷的发生。HOP/NECC1对分化刺激的逐渐诱导可能导致决定分化为特定类型的滋养层细胞谱系，并导致非致死性缺陷，如HOP/NECC1(-/-)胎盘。
Homeodomain-only protein/ not expressed in choriocarcinoma clone 1 ( HOP/ NECC1) is a newly identified gene that modifies the expression of cardiac- specific genes and thereby regulates heart development. More recently, HOP/ NECC1 was reported to be a suppressor of choriocarcinogenesis. Here, we examined the temporal expression profile of HOP/ NECC1 in wild- type mouse placenta. We found that E8.5 - E9.5 wild- type placenta expressed HOP/ NECC1 in the giant cell and spongiotrophoblast layers. HOP/ NECC1 ( -/- ) placenta exhibited marked propagation of giant cell layers and, in turn reduction of spongiotrophoblast formation. We demonstrated SRF transcriptional activity increased in the differentiating trophoblasts and forced expression of SRF in a trophoblast stem ( TS) cell line induces the differentiation into giant cells. Negative regulation of SRF ( serum response factor) by the binding of HOP/ NECC1 protein contributed at least in part to the generation of these placental defects. Gradual induction of HOP/ NECC1 in response to differentiation stimuli may result in the decision to differentiate into a particular type of trophoblastic cell lineage and result in non- lethal defects shown by the HOP/ NECC1 ( -/- ) placentas.