An in vitro stem cell model of human epiblast and yolk sac interaction

eLife

Kirsty ML Mackinlay¹  George Hudson¹  Bailey AT Weatherbee¹  Charlotte E Handford²  Marta N Shahbazi³  Viviane Souza Rosa⁴  Magdalena Zernicka-Goetz⁵  Lygia V Pereira⁶  Tim Coorens⁷  Sam Behjati⁷  Ludovic Vallier⁸ 

[1] Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom;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;MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;Synthetic Mouse and Human Embryology Group, California Institute of Technology (Caltech), Division of Biology and Biological Engineering, Pasadena, United States;National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil;Wellcome Sanger Institute, Cambridge, United Kingdom;Wellcome – MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom;

关键词: embryology;    stem cells;    hypoblast;    human development;    pluripotency;    epiblast;    Human;    Mouse;   

DOI  :  10.7554/eLife.63930

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY