利用胚胎模型理解胚胎谱系的发育与进展:聚焦于原始生殖细胞的发育
Using Embryo Models to Understand the Development and Progression of Embryonic Lineages: A Focus on Primordial Germ Cell Development.
作者信息
Rodriguez-Polo Ignacio, Moris Naomi
机构信息
The Francis Crick Institute, London, UK.
出版信息
Cells Tissues Organs. 2024;213(6):503-522. doi: 10.1159/000538275. Epub 2024 Mar 13.
BACKGROUND
Recapitulating mammalian cell type differentiation in vitro promises to improve our understanding of how these processes happen in vivo, while bringing additional prospects for biomedical applications. The establishment of stem cell-derived embryo models and embryonic organoids, which have experienced explosive growth over the last few years, opens new avenues for research due to their scale, reproducibility, and accessibility. Embryo models mimic various developmental stages, exhibit different degrees of complexity, and can be established across species. Since embryo models exhibit multiple lineages organized spatially and temporally, they are likely to provide cellular niches that, to some degree, recapitulate the embryonic setting and enable "co-development" between cell types and neighbouring populations. One example where this is already apparent is in the case of primordial germ cell-like cells (PGCLCs).
SUMMARY
While directed differentiation protocols enable the efficient generation of high PGCLC numbers, embryo models provide an attractive alternative as they enable the study of interactions of PGCLCs with neighbouring cells, alongside the regulatory molecular and biophysical mechanisms of PGC competency. Additionally, some embryo models can recapitulate post-specification stages of PGC development (including migration or gametogenesis), mimicking the inductive signals pushing PGCLCs to mature and differentiate and enabling the study of PGCLC development across stages. Therefore, in vitro models may allow us to address questions of cell type differentiation, and PGC development specifically, that have hitherto been out of reach with existing systems.
KEY MESSAGE
This review evaluates the current advances in stem cell-based embryo models, with a focus on their potential to model cell type-specific differentiation in general and in particular to address open questions in PGC development and gametogenesis.
背景
在体外重现哺乳动物细胞类型分化,有望增进我们对这些过程在体内如何发生的理解,同时为生物医学应用带来更多前景。干细胞衍生的胚胎模型和胚胎类器官在过去几年经历了爆炸式增长,因其规模、可重复性和可及性为研究开辟了新途径。胚胎模型模拟各种发育阶段,展现出不同程度的复杂性,并且可以跨物种建立。由于胚胎模型呈现出在空间和时间上组织起来的多种谱系,它们很可能提供在某种程度上重现胚胎环境并使细胞类型与相邻群体之间能够“共同发育”的细胞龛。这一点已经很明显的一个例子是原始生殖细胞样细胞(PGCLC)的情况。
总结
虽然定向分化方案能够高效产生大量的PGCLC,但胚胎模型提供了一个有吸引力的替代方案,因为它们能够研究PGCLC与相邻细胞的相互作用,以及PGC能力的调节分子和生物物理机制。此外,一些胚胎模型可以重现PGC发育的指定后阶段(包括迁移或配子发生),模拟促使PGCLC成熟和分化的诱导信号,并能够研究PGCLC跨阶段的发育。因此,体外模型可能使我们能够解决细胞类型分化问题,特别是PGC发育问题,而这些问题是现有系统迄今无法解决的。
关键信息
本综述评估了基于干细胞的胚胎模型的当前进展,重点关注它们在模拟一般细胞类型特异性分化方面的潜力,特别是解决PGC发育和配子发生中悬而未决问题的潜力。