Examining the State of the Science of Mammalian Embryo Model Systems Proceedings of a Workshop (2020) / Chapter Skim
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6 Exploring Opportunities and Challenges with Mammalian Embryo Model Systems
6 Exploring Opportunities and Challenges with Mammalian Embryo Model Systems
Pages 99-106
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From page 99... ...
Two fundamental questions about embryo models that remain unanswered were highlighted: the developmental status of human pluripotent stem cells and the stage of mammalian development that these cells most closely resemble. Understanding pluripotent cells in a developmental context is important for (1)
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From page 100... ...
He calls this a "stable attractor" state because regardless of whether the lines are made from the human teratocarcinoma, an embryo, or from reprogramming, under a wide range of culture conditions they revert and settle into this particular state, which is the conventional human stem cell. Assessment of the developmental status of human pluripotent cells is complicated by heterogeneity in cultures, as it was originally in the mouse, and there are subpopulations of pluripotent cells within the human cultures with distinct biological properties and gene expression (Kolle et al., 2009; Laslett et al., 2007)
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From page 101... ...
Self-renewing hPSCs do not resemble mouse epiblast stem cells and are not primed for any particular fate, he added. When the embryo implants in the mouse, the epiblast cells are no longer capable of differentiating to extraembryonic trophoblast or primitive endoderm.
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From page 102... ...
He suggested that, in principle, nonhuman primate embryos could be cultured to establish benchmarks for calibrating in vitro human stem cell models. Golos suggested analyzing archived material from nonhuman primates for markers that are being discovered in extended culture or pluripotent cell studies.
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From page 103... ...
Brivanlou went on to question the extent to which human or primate embryological work can be rationalized or justified based on utilitarian grounds versus the desire for basic knowledge. In his experience, he said, support and funding are not generally forthcoming in response to arguments based on the need to understand our human origins; utilitarian arguments based on the potential to cure disease, for example, tend to be more effective.
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From page 104... ...
That knowledge could then be used to understand how, in the human context, embryonic ectoderm drives epiblast gastrulation and primordial germ cells develop in the embryonic ectoderm compartment. Synthetic models provide experimental systems for studying those fundamental biological questions, which was not possible in the past, Fu said.
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From page 105... ...
Regarding stem cells themselves, much remains to be understood about the state of those cells and how to maintain those states in the desired way. "We are not making human embryos in a dish; we are not making test tube babies; we are not generating anything that could in any way be considered as viable human embryos, nor is that the intent of the any of the research that you heard about today," Rossant emphasized.
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