State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
J Reprod Dev. 2021 Apr 21;67(2):89-97. doi: 10.1262/jrd.2020-107. Epub 2021 Jan 15.
Depletion of hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor (c-Met) in mice leads to fetal lethality and placental maldevelopment. However, the dynamic change pattern of HGF/c-Met signaling during placental development and its involvement in the early differentiation of trophoblasts remain to be elucidated. In this study, using in situ hybridization assay, we elaborately demonstrated the spatial-temporal expression of Hgf and c-Met in mouse placenta from E5.5, the very early stage after embryonic implantation, to E12.5, when the placental structure is well developed. The concentration of the soluble form of c-Met (sMet) in maternal circulation peaked at E10.5. By utilizing the induced differentiation model of mouse trophoblast stem cells (mTSCs), we found that HGF significantly promoted mTSC differentiation into syncytiotrophoblasts (STBs) and invasive parietal trophoblast giant cells (PTGCs). Interestingly, sMet efficiently reversed the effect of HGF on mTSC differentiation. These findings indicate that HGF/c-Met signaling participates in regulating placental trophoblast cell fate at the early differentiation stage and that sMet acts as an endogenous antagonist in this aspect.
肝细胞生长因子 (HGF) 或间质上皮转化因子 (c-Met) 在小鼠中的耗竭会导致胎儿致死和胎盘发育不良。然而，HGF/c-Met 信号在胎盘发育过程中的动态变化模式及其在滋养层早期分化中的作用仍有待阐明。在这项研究中，我们使用原位杂交检测，详细展示了 Hgf 和 c-Met 在小鼠胎盘从胚胎植入后的非常早期 E5.5 到 E12.5 期间的时空表达，此时胎盘结构发育良好。母血中可溶性 c-Met (sMet) 的浓度在 E10.5 时达到峰值。通过利用小鼠滋养层干细胞 (mTSC) 的诱导分化模型，我们发现 HGF 可显著促进 mTSC 分化为合体滋养层细胞 (STB) 和侵袭性壁层滋养层 giant 细胞 (PTGC)。有趣的是，sMet 有效地逆转了 HGF 对 mTSC 分化的作用。这些发现表明，HGF/c-Met 信号参与调节早期分化阶段胎盘滋养层细胞的命运，而 sMet 在这方面起内源性拮抗剂的作用。
