利用长期体外胚胎培养技术解析灵长类动物早期胚胎植入后的发育过程。
Dissecting primate early post-implantation development using long-term in vitro embryo culture.
机构信息
Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
出版信息
Science. 2019 Nov 15;366(6467). doi: 10.1126/science.aaw5754. Epub 2019 Oct 31.
The transition from peri-implantation to gastrulation in mammals entails the specification and organization of the lineage progenitors into a body plan. Technical and ethical challenges have limited understanding of the cellular and molecular mechanisms that underlie this transition. We established a culture system that enabled the development of cynomolgus monkey embryos in vitro for up to 20 days. Cultured embryos underwent key primate developmental stages, including lineage segregation, bilaminar disc formation, amniotic and yolk sac cavitation, and primordial germ cell-like cell (PGCLC) differentiation. Single-cell RNA-sequencing analysis revealed development trajectories of primitive endoderm, trophectoderm, epiblast lineages, and PGCLCs. Analysis of single-cell chromatin accessibility identified transcription factors specifying each cell type. Our results reveal critical developmental events and complex molecular mechanisms underlying nonhuman primate embryogenesis in the early postimplantation period, with possible relevance to human development.
哺乳动物从着床期到原肠胚期的转变需要将谱系祖细胞特化并组织成一个体节计划。技术和伦理方面的挑战限制了对这一转变所涉及的细胞和分子机制的理解。我们建立了一种培养体系,使食蟹猴胚胎能够在体外发育长达 20 天。培养的胚胎经历了关键的灵长类动物发育阶段,包括谱系分离、双层盘形成、羊膜和卵黄囊腔化以及原始生殖细胞样细胞 (PGCLC) 分化。单细胞 RNA 测序分析揭示了原始内胚层、滋养外胚层、上胚层谱系和 PGCLC 的发育轨迹。单细胞染色质可及性分析鉴定了指定每种细胞类型的转录因子。我们的研究结果揭示了非人类灵长类动物早期着床后胚胎发生的关键发育事件和复杂分子机制,这可能与人类发育有关。