Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Nature. 2016 Sep 1;537(7618):57-62. doi: 10.1038/nature19096. Epub 2016 Aug 24.
The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre- and post-implantation EPI development in cynomolgus monkeys (Macaca fascicularis). We show that after specification in the blastocysts, EPI from cynomolgus monkeys (cyEPI) undergoes major transcriptome changes on implantation. Thereafter, while generating gastrulating cells, cyEPI stably maintains its transcriptome over a week, retains a unique set of pluripotency genes and acquires properties for 'neuron differentiation'. Human and monkey pluripotent stem cells show the highest similarity to post-implantation late cyEPI, which, despite co-existing with gastrulating cells, bears characteristics of pre-gastrulating mouse EPI and epiblast-like cells in vitro. These findings not only reveal the divergence and coherence of EPI development, but also identify a developmental coordinate of the spectrum of pluripotency among key species, providing a basis for better regulation of human pluripotency in vitro.
上胚层（EPI）是哺乳动物所有体细胞和生殖细胞以及体外多能干细胞的起源。为了探索人和灵长类动物多能性的发生，我们对食蟹猴（Macaca fascicularis）胚胎植入前和植入后 EPI 发育进行了全面的单细胞 RNA 测序。我们表明，在上胚层形成之后，食蟹猴的 EPI（cyEPI）在植入时经历了主要的转录组变化。此后，在产生原肠胚细胞的同时，cyEPI 在一周多的时间内稳定地保持其转录组，保留了一组独特的多能性基因，并获得了“神经元分化”的特性。人和猴的多能干细胞与植入后的晚期 cyEPI 最为相似，尽管与原肠胚细胞共存，但具有预原肠胚小鼠 EPI 和体外类胚层细胞的特征。这些发现不仅揭示了 EPI 发育的分歧和一致性，而且确定了关键物种中多能性谱的一个发育坐标，为更好地体外调控人类多能性提供了基础。
