Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom.
Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom.
Curr Top Dev Biol. 2018;128:295-338. doi: 10.1016/bs.ctdb.2017.11.004. Epub 2018 Feb 13.
Understanding the progression of early human embryonic development prior to implantation is of fundamental biological importance. Greater insights into early developmental events may lead to clinical improvements, not only via the establishment of novel stem cell models with increased potential or more physiological relevance, but also by uncovering some underlying causes of infertility, miscarriages, and developmental disorders. The majority of human embryos available for study are those donated to research once they are surplus to family building following in vitro fertilization, though in some countries it is also possible to create embryos using donated gametes. As human embryo development is surprisingly inefficient, with only 40% reaching the blastocyst stage in vitro (French, Sabanegh, Goldfarb, & Desai, 2010; Gardner, Lane, Stevens, Schlenker, & Schoolcraft, 2000), many embryos may not develop to a stage suitable for study. Where legally permitted, the oversight of human embryo research is subject to either ethics approval from a local institutional review board (i.e., China and the United States) or both a national regulator as well as a regional research ethics committee (i.e., the United Kingdom). The study of human development has historically been by necessity comparative, relying on model organisms and stem cell lines to inform analyses. Preimplantation mouse and human embryos in particular exhibit remarkably similar gross morphologies at these early stages of development, although key differences have been identified in gene expression patterns and developmental timing. While recent advances in high-resolution transcriptomic analyses at the single cell level have improved our capability to interrogate expression patterns directly in the human embryo, we still lack an understanding of basic molecular events in the human embryo, including how the first cell lineages become specified. Here, we present a current overview of the major developmental events during human preimplantation development, from fertilization to delineation of the embryonic and extraembryonic lineages prior to implantation. Comparisons to both the mouse and alternative models are included where these have formed the basis for similar investigations in a human context.
理解着床前早期人类胚胎发育的进程具有基础生物学意义。对早期发育事件的深入了解不仅可以通过建立具有更高潜力或更接近生理相关性的新型干细胞模型来改善临床效果，还可以揭示不孕、流产和发育障碍的一些潜在原因。可供研究的大多数人类胚胎是在体外受精后家庭生育不需要的胚胎捐赠给研究使用的，尽管在一些国家也可以使用捐赠的配子来创建胚胎。由于人类胚胎发育的效率非常低，只有 40%的胚胎在体外达到囊胚阶段（French、Sabanegh、Goldfarb 和 Desai，2010；Gardner、Lane、Stevens、Schlenker 和 Schoolcraft，2000），因此许多胚胎可能无法发育到适合研究的阶段。在法律允许的情况下，人类胚胎研究的监督要么需要当地机构审查委员会（例如中国和美国）的伦理批准，要么需要国家监管机构和地区伦理委员会（例如英国）的双重批准。人类发育的研究历史上一直是比较性的，依赖于模式生物和干细胞系来提供分析信息。特别是在这些早期发育阶段，植入前的小鼠和人类胚胎表现出非常相似的大体形态，尽管在基因表达模式和发育时间上已经确定了关键差异。尽管最近在单细胞水平的高分辨率转录组分析方面取得了进展，提高了我们直接在人类胚胎中探究表达模式的能力，但我们仍然缺乏对人类胚胎基本分子事件的理解，包括第一个细胞谱系如何被指定。在这里，我们介绍了人类植入前胚胎发育过程中的主要发育事件概述，从受精到胚胎和胚胎外谱系的划定，直至植入前。在人类背景下，对类似研究的基础是包括小鼠和其他模型在内的比较研究，因此也包括了与这些模型的比较。
