Wu Zhao, Zhang Wei, Chen Guibin, Cheng Lu, Liao Jing, Jia Nannan, Gao Yuan, Dai Huiming, Yuan Jinduo, Cheng Linzhao, Xiao Lei
Laboratory of Molecular Cell Biology, Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, the Cell Bank/Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
J Biol Chem. 2008 Sep 5;283(36):24991-5002. doi: 10.1074/jbc.M803893200. Epub 2008 Jul 2.
Cell fate commitment of pre-implantation blastocysts, to either the inner cell mass or trophoblast, is the first step in cell lineage segregation of the developing human embryo. However, the intercellular signals that control fate determination of these cells remain obscure. Human embryonic stem cells (hESCs) provide a unique model for studying human early embryonic development. We have previously shown that Activin/Nodal signaling contributes to maintaining pluripotency of hESCs, which are derivatives of the inner cell mass. Here we further demonstrate that the inhibition of Activin/Nodal signaling results in the loss of hESC pluripotency and trophoblast differentiation, similar to BMP4-induced trophoblast differentiation from hESCs. We also show that the trophoblast induction effect of BMP4 correlates with and depends on the inhibition of Activin/Nodal signaling. However, the activation of BMP signaling is still required for trophoblast differentiation when Activin/Nodal signaling is inhibited. These data reveal that the early lineage segregation of hESCs is determined by the combinatorial signals of Activin/Nodal and BMP.
植入前囊胚向内细胞团或滋养层的细胞命运决定是发育中的人类胚胎细胞谱系分离的第一步。然而，控制这些细胞命运决定的细胞间信号仍不清楚。人类胚胎干细胞（hESC）为研究人类早期胚胎发育提供了一个独特的模型。我们之前已经表明，激活素/节点信号有助于维持hESC的多能性，hESC是内细胞团的衍生物。在这里，我们进一步证明，抑制激活素/节点信号会导致hESC多能性丧失和滋养层分化，类似于BMP4诱导hESC向滋养层分化。我们还表明，BMP4的滋养层诱导作用与激活素/节点信号的抑制相关并依赖于此。然而，当激活素/节点信号被抑制时，滋养层分化仍需要BMP信号的激活。这些数据表明，hESC的早期谱系分离是由激活素/节点和BMP的组合信号决定的。
