An in vitro stem cell model of human epiblast and yolk sac interaction.
An in vitro stem cell model of human epiblast and yolk sac interaction.
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人育细胞和蛋黄囊相互作用的体外干细胞模型。
DOI：
10.7554/elife.63930
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发表时间：
2021-08-17
期刊：
影响因子：
7.7
通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
--
作者：
Mackinlay KM;Weatherbee BA;Souza Rosa V;Handford CE;Hudson G;Coorens T;Pereira LV;Behjati S;Vallier L;Shahbazi MN;Zernicka-Goetz M
人类胚胎发生需要胚胎和胚胎外细胞之间复杂的信号相互作用。然而，由于缺乏相关的干细胞模型，胚胎外细胞如何指导人类胚胎内的形态发生在很大程度上仍然是未知的。在这里，我们已经建立了条件，以分化成卵黄囊样细胞（YSLCs），类似于植入后的人类下胚层的分子和功能的人多能干细胞（hPSC）。YSLC诱导人胚胎干细胞（hESC）中的多能性和前外胚层标志物的表达，而中胚层和内胚层标志物的表达则以牺牲为代价。这种活性是由BMP和WNT信号通路抑制剂的释放介导的，因此，类似于小鼠胚胎的前内脏内胚层信号中心的功能，其建立了前后轴。我们的研究结果暗示卵黄囊在人类胚胎的上胚层细胞命运的规范，并建议YSLCs作为一种工具，研究植入后的人类胚胎体外发育。
Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.