Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and are capable of contributing to intra- or inter-species chimeras in vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.

动态多能干细胞（PSC）状态是体内多能连续体的体外适应。先前的研究已经产生了许多具有不同性质的PSC。但是，迄今为止，尚无已知的PSC表现出嵌合体形成的双重能力和对原始生殖细胞（PGC）规格的直接反应，而PGC是形成性多能性的独特功能。在这里，通过调节成纤维细胞生长因子（FGF），转化生长因子β（TGF-β）和WNT途径，我们从小鼠，马和人（称为XPSC）中衍生了PSC，这些PSC可以直接诱导类似PGC的细胞体外并能够在体内促成种内或种间嵌合体。XPSCs代表介于幼稚和引发多能性之间的多能性状态，并具有形成性多能性的特征性分子，细胞和表型特征。XPSC为研究哺乳动物的多能性和剖析控制PGC规范的分子机制开辟了新途径。我们的方法可能广泛适用于从其他哺乳动物物种衍生出类似的干细胞。