摘要

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.

动态的多能干细胞 (PSC) 状态是体内多能性连续体的体外适应。以前的研究已经产生了许多具有不同特性的 PSC。然而，迄今为止，还没有已知的 PSC 表现出双重能力，即嵌合体形成和对原始生殖细胞 (PGC) 分化的直接反应性，这是formative多能性的独特功能特征。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 通路，我们从小鼠、马和人类（称为 XPSCs）中获得了允许直接诱导 PGC 样细胞的 PSC并且能够在体内促成种内或种间嵌合体。XPSC 代表了介于naive多能性和primed多能性之间的多能性状态，并具有formative多能性的分子、细胞和表型特征。XPSCs 开辟了研究哺乳动物多能性和剖析控制 PGC 分化的分子机制的新途径。我们的方法可能广泛适用于从其他哺乳动物物种中提取类似的干细胞。

笔记

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