Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom.
National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Elife. 2021 Aug 17;10:e63930. doi: 10.7554/eLife.63930.
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
人类胚胎发生涉及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，胚胎外细胞如何在人类胚胎中指导形态发生在很大程度上仍是未知的。在这里，我们已经建立了条件，将人类多能干细胞（hPSCs）分化为卵黄囊样细胞（YSLCs），这些细胞在分子和功能上类似于植入后人类下胚层。YSLCs 在 hESCs 中诱导多能性和前外胚层标记物的表达，而牺牲中胚层和内胚层标记物。这种活性是通过释放 BMP 和 WNT 信号通路抑制剂来介导的，因此类似于小鼠胚胎中前内脏内胚层信号中心的功能，该中心建立了前后轴。我们的结果表明卵黄囊在人类胚胎中胚外细胞命运特化中的作用，并提出 YSLCs 作为研究植入后人类胚胎发育的工具。
