The dual roles of geminin during trophoblast proliferation and differentiation.
The dual roles of geminin during trophoblast proliferation and differentiation.
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DOI：
10.1016/j.ydbio.2013.12.034
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发表时间：
2014-03-01
影响因子：
2.7
通讯作者：
DePamphilis, Melvin L.
中科院分区：
文献类型：
--
作者：
de Renty, Christelle;Kaneko, Kotaro J.;DePamphilis, Melvin L.
关键词：
双生蛋白是一种同时参与DNA复制和细胞命运获取的蛋白质。虽然它对哺乳动物着床前发育是必不可少的，但它的作用尚不清楚。在一项研究中，去除小鼠着床前胚胎中的gminin基因(Gmnn)导致了细胞凋亡，这表明ginin阻止了DNA的重新复制，而在另一项研究中，它导致了卵裂球向滋养层巨细胞(TGC)的分化，这表明ginin调节滋养层细胞的规格和分化。其他研究得出结论，滋养层细胞分化为TGCs受成纤维细胞生长因子-4(FGF4)的调节，而Geminin是维持内周期所必需的。在这里，我们表明，在FGF4存在下增殖的滋养层干细胞(TSCs)中的Gmnn的消融与FGF4剥夺所触发的事件非常相似：细胞增殖停止，形成巨细胞，在没有DNA损伤和凋亡的情况下过度DNA复制，以及基因表达的变化，包括Chk1的丢失和p57和p21的上调。此外，剥夺TSCs的FGF4使Ginin降低到维持TGCs内周期所需的基础水平。因此，双黄素既是调控滋养层细胞增殖和分化的FGF4信号转导途径的一个组成部分，又是维持内周期所必需的。
Geminin is a protein involved in both DNA replication and cell fate acquisition. Although it is essential for mammalian preimplantation development, its role remains unclear. In one study, ablation of the geminin gene (Gmnn) in mouse preimplantation embryos resulted in apoptosis, suggesting that geminin prevents DNA re-replication, whereas in another study it resulted in differentiation of blastomeres into trophoblast giant cells (TGCs), suggesting that geminin regulates trophoblast specification and differentiation. Other studies concluded that trophoblast differentiation into TGCs is regulated by fibroblast growth factor-4 (FGF4), and that geminin is required to maintain endocycles. Here we show that ablation of Gmnn in trophoblast stem cells (TSCs) proliferating in the presence of FGF4 closely mimics the events triggered by FGF4 deprivation: arrest of cell proliferation, formation of giant cells, excessive DNA replication in the absence of DNA damage and apoptosis, and changes in gene expression that include loss of Chk1 with up-regulation of p57 and p21. Moreover, FGF4 deprivation of TSCs reduces geminin to a basal level that is required for maintaining endocycles in TGCs. Thus, geminin acts both like a component of the FGF4 signal transduction pathway that governs trophoblast proliferation and differentiation, and geminin is required to maintain endocycles.
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影响因子：
4.5
作者：
Ding Q;MacAlpine DM
通讯作者：
MacAlpine DM
影响因子：
2.1
作者：
Hara, Kentaro;Nakayama, Keiichi I.;Nakayama, Keiko
通讯作者：
Nakayama, Keiko
DOI：
10.1242/dev.068676
发表时间：
2012-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Kisielewska J;Blow JJ
通讯作者：
Blow JJ
影响因子：
64.5
作者：
Geng, Y;Yu, QY;Sicinski, P
通讯作者：
Sicinski, P
影响因子：
5.3
作者：
Dahl, KDC;Fryer, BH;Simon, MC
通讯作者：
Simon, MC