ETS1 induces human trophoblast differentiation.
ETS1 induces human trophoblast differentiation.
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DOI：
10.1210/en.2014-1760
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发表时间：
2015-02
期刊：
影响因子：
4.8
通讯作者：
C. Kessler;J. Stanek;K. Stringer;S. Handwerger
中科院分区：
文献类型：
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作者：
C. Kessler;J. Stanek;K. Stringer;S. Handwerger
利用高度浓缩的人单核细胞滋养层细胞(CTB)在体外自发分化为多核合体滋养层细胞(STB)表型，研究了转录因子v-ETS禽红母细胞增殖症病毒E26癌基因同源1(ETS1)在人滋养层细胞分化中的可能作用。在新分离的CTB中，ETS1mRNA和蛋白水平丰富，并随着细胞的分化而降低。桥粒蛋白染色显示，在新制备的CTB中沉默ETS1的表达显著地减弱了合胞化，并阻断了合胞素、转录因子激活蛋白-2α、胎盘催乳素和其他STB特异性基因的诱导。相反，ETS1在原代滋养层细胞中的过表达诱导了STB标记基因的mRNAs，并反式激活了每个基因近端的启动子。综上所述，这些发现强烈表明ETS1在诱导人绒毛CTB分化中起着关键作用。Ets1对合胞化的影响可能至少部分是由于抑制了合胞素的表达，而STB标志基因的诱导可能部分是由于激活蛋白-2α的反式激活。
A possible role for the transcription factor v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1) in human trophoblast cell differentiation was examined using a highly enriched fraction of human mononuclear cytotrophoblast cells (CTBs) that differentiate spontaneously in vitro to a multinucleated syncytiotrophoblast cell (STB) phenotype. ETS1 mRNA and protein levels were abundant in freshly isolated CTBs and decreased as the cells differentiated. Silencing of ETS1 expression in freshly prepared CTBs markedly attenuated syncytialization, as demonstrated by desmoplakin staining, and blocked the induction of syncytin, the transcription factor activator protein-2α, placental lactogen, and other STB-specific genes. Conversely, overexpression of ETS1 in primary trophoblast cells induced STB marker gene mRNAs and transactivated each of the gene proximal promoters. Taken together, these findings strongly suggest a critical role for ETS1 in the induction of human villus CTB differentiation. The effect of ETS1 on syncytialization likely results, at least in part, from inhibition of syncytin expression, whereas the induction of STB marker genes likely results in part from transactivation by activator protein-2α.