Examining the State of the Science of Mammalian Embryo Model Systems Proceedings of a Workshop (2020) / Chapter Skim
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1 Introduction and Overview
1 Introduction and Overview
Pages 1-10
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. The use of embryo models to study human embryogenesis can contribute new knowledge about an essential stage of human development that is otherwise inaccessible (see the section on the Current State of Regulation of Research on Human Embryo Models in Hyun et al., 2020)
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Presentations and discussions covered topics such as the characteristics of advanced mammalian embryo model systems, the differences between various mammalian embryo model systems and bona fide mammalian embryos, and the differences between mammalian embryo model systems and mammalian "embryoid bodies," which arise via aggregation of stem cells but do not recapitulate regular organization. Participants considered whether embryo model systems -- especially those that use nonhuman primate cells -- can be used to predict the function of systems made with human cells.
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However, she said, embarking on this human model pathway will require careful consideration of the similarities and differences between mouse and human systems in order to select the appropriate cell type for developing human models. Furthermore, it will require aligning directly with events in the human embryo itself, either via culture in vitro or in comparison with nonhuman primate models.
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signaling pathways are critical to final cell fate specification in the mouse blastocyst. Less information is available on blastocyst lineage commitment in humans, although some studies suggest that human early blastocyst cells remain uncommitted to lineage (De Paepe et al., 2013)
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The use of human embryos can be considered ethically challenging in many regions, while nonhuman primate embryos are expensive and only available in limited research centers. These challenges have led researchers to replace human embryos with selforganizing stem cell model systems in order to study development without the use of embryos.
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. Several laboratories have derived extended-potential stem cells that are purported to be able to generate extraembryonic tissues themselves; because they have an extended potential beyond pluripotent cells, they can generate epiblast and primitive endoderm when combined with TSCs to make a blastoid (Sozen et al., 2019)
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Differences Between Mouse and Human Stem Cells Rossant highlighted several differences between mouse and human stem cells. Although it appears that human naïve ESCs can be cultured in conditions similar to those used for mouse cells, the lineage status of the human cells is less clear.
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Speakers discussed the molecular mechanisms of lineage specification in human embryos, described the development of embryo models, and considered the clinical implications of modeling pre-implantation embryo development. Chapter 3 examines the development of extraembryonic lineages and the impact of those lineages on human embryo model systems, featuring presentations on modeling trophoblast differentiation using pluripotent stem cells and molecular innovation in the human trophoblast lineage.
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Chapter 5 summarizes the workshop session on comparative embryonic development across species. Speakers explored mechanisms underlying pre-implantation chromosomal instability, systems to differentiate trophoblast from primate pluripotent cells, models of early neural crest formation in humans, and models of pre-implantation development generated from pluripotent stem cells with expanded potential.
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