MTA3 regulates differentiation of human cytotrophoblast stem cells.
MTA3 regulates differentiation of human cytotrophoblast stem cells.
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DOI：
10.1016/j.placenta.2015.07.122
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发表时间：
2015-09
期刊：
影响因子：
3.8
通讯作者：
Parast MM
中科院分区：
文献类型：
--
作者：
Horii M;Moretto-Zita M;Nelson KK;Li Y;Parast MM
早期胎盘发育取决于细胞滋养层（CTB）增殖和分化的正确平衡，既可以分化为参与营养/气体交换的合胞体滋养层（STB），也可以分化为参与建立胎盘血流的浸润性绒毛外滋养层（EVT）。转移相关蛋白-3（MTA 3）是一种转录辅阻遏物，已知可调节细胞迁移。此外，据报道，MTA 3在先兆子痫中减少。我们着手研究MTA 3在人类滋养层细胞分化中的作用。我们用MTA 3抗体和其他滋养层标记物对孕早期和孕晚期胎盘切片进行共染色。我们还评估了原代分离的CTB体外分化后MTA 3的表达。为了评估MTA 3在滋养层分化中的作用，我们使用慢病毒构建体来过表达和敲低其表达。滋养层细胞分化的标志物表达和功能测定，包括hCG ELISA和细胞迁移的组合进行了评估。MTA 3在人胎盘的CTB和近端细胞柱EVT中大量表达，并随着进一步分化为STB和成熟EVT而降低。JEG 3中的MTA 3敲低导致STB标记物、CGB和GCM 1以及hCG分泌减少2-3倍。在EVT分化方面，MTA 3敲低导致HLA-G和细胞迁移增加1.5-2倍，但降低了成熟EVT标志物ITGA 1。总之，我们的数据表明，MTA 3在终末滋养细胞分化为hCG分泌STB和成熟EVT中的作用。
Early placental development depends on the correct balance of cytotrophoblast (CTB) proliferation and differentiation, into either syncytiotrophoblast (STB) involved in nutrient/gas exchange, or invasive extravillous trophoblast (EVT) involved in establishment of blood flow to the placenta. Metastasis associated protein-3 (MTA3) is a transcriptional co-repressor known to regulate cell migration. In addition, MTA3 is reportedly decreased in preeclampsia. We set out to investigate the role of MTA3 in human trophoblast differentiation. We co-stained first and third trimester placental sections with antibodies to MTA3 and other trophoblast markers. We also evaluated MTA3 expression following in vitro differentiation of primary isolated CTB. In order to evaluate the role of MTA3 in trophoblast differentiation, we used lentiviral constructs to overexpress and knock down its expression. Trophoblast differentiation was assessed by a combination of marker expression and functional assays, including hCG ELISA and cell migration. MTA3 was abundantly expressed in CTB and proximal cell column EVT in the human placenta and decreased with further differentiation into STB and mature EVT. MTA3 knockdown in JEG3 resulted in a 2–3 fold decrease in STB markers, CGB and GCM1, as well as in hCG secretion. In terms of EVT differentiation, MTA3 knockdown led to a 1.5–2 fold increase in HLA-G and cell migration, but decreased the mature EVT marker ITGA1. Taken together, our data suggest a role for MTA3 in terminal trophoblast differentiation into both hCG-secreting STB and mature EVT.