Mouse and Human Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge, CB2 3EG, UK.
Plasticity and Synthetic Embryology Group, California Institute of Technology, Division of Biology and Biological Engineering, 1200 E. California Boulevard, Pasadena, CA, 91125, USA.
Dev Biol. 2021 Jun;474:91-99. doi: 10.1016/j.ydbio.2020.12.010. Epub 2020 Dec 24.
Early human post-implantation development involves extensive growth combined with a series of complex morphogenetic events. The lack of precise spatial and temporal control over these processes leads to pregnancy loss. Given the ethical and technical limitations in studying the natural human embryo, alternative approaches are needed to investigate mechanisms underlying this critical stage of human development. Here, we present an overview of the different stem cells and stem cell-derived models which serve as useful, albeit imperfect, tools in understanding human embryogenesis. Current models include stem cells that represent each of the three earliest lineages: human embryonic stem cells corresponding to the epiblast, hypoblast-like stem cells and trophoblast stem cells. We also review the use of human embryonic stem cells to model complex aspects of epiblast morphogenesis and differentiation. Additionally, we propose that the combination of both embryonic and extra-embryonic stem cells to form three-dimensional embryo models will provide valuable insights into cell-cell chemical and mechanical interactions that are essential for natural embryogenesis.
早期人类胚胎着床后发育涉及广泛的生长,同时伴随着一系列复杂的形态发生事件。由于对这些过程缺乏精确的时空控制,导致妊娠丢失。考虑到研究自然人类胚胎在伦理和技术上的限制,需要寻找替代方法来研究人类发育这一关键阶段的机制。在这里,我们概述了不同的干细胞和由干细胞衍生而来的模型,它们在理解人类胚胎发生过程中是有用的,尽管并不完美。目前的模型包括代表三个最早谱系的干细胞:对应于上胚层的人类胚胎干细胞、类胚下干细胞和滋养层干细胞。我们还回顾了利用人类胚胎干细胞来模拟上胚层形态发生和分化的复杂方面。此外,我们提出将胚胎和胚胎外干细胞结合起来形成三维胚胎模型,将为理解对自然胚胎发生至关重要的细胞间化学和机械相互作用提供有价值的见解。