A developmental coordinate of pluripotency among mice, monkeys and humans
A developmental coordinate of pluripotency among mice, monkeys and humans
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DOI：
10.1038/nature19096
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发表时间：
2016-09-01
期刊：
影响因子：
64.8
通讯作者：
Saitou, Mitinori
中科院分区：
文献类型：
--
作者：
Nakamura, Tomonori;Okamoto, Ikuhiro;Saitou, Mitinori
外胚层（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来源。为了探索人类和灵长类动物多能性的个体发育，在这里，我们对食蟹猴（Macacafascicularis）植入前和植入后EPI发育进行了全面的单细胞RNA测序。我们发现，在囊胚中的规范后，从食蟹猴（cyEPI）的EPI经历了重大的转录组的变化植入。此后，在产生原肠胚细胞的同时，cyEPI稳定地保持其转录组超过一周，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。人和猴多能干细胞显示出与植入后晚期cyEPI的最高相似性，尽管与原肠胚细胞共存，但其具有体外原肠胚形成前小鼠EPI和外胚层样细胞的特征。这些发现不仅揭示了EPI发育的差异性和一致性，而且还确定了关键物种之间多能性谱的发育坐标，为更好地调控体外人类多能性提供了基础。
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 (Macacafascicularis). 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.