Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification
Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification
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DOI：
10.1016/j.stem.2020.11.003
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发表时间：
2021-03-04
期刊：
影响因子：
23.9
通讯作者：
Wu, Jun
中科院分区：
文献类型：
--
作者：
Yu, Leqian;Wei, Yulei;Wu, Jun
动态多能干细胞（PSC）状态是体内多能性连续体的体外适应。先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表现出嵌合体形成和对原始生殖细胞（PGC）特化的直接响应的双重能力，这是形成性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途径，我们从小鼠，马和人（指定为XPSC）中获得PSC，这些PSC允许体外直接诱导PGC样细胞，并能够促进体内种内或种间嵌合体。XPSC代表幼稚多能性和引发多能性之间的多能性状态，并且具有形成多能性的分子、细胞和表型特征。XPSC为研究哺乳动物多能性和剖析PGC特化的分子机制开辟了新途径。我们的方法可以广泛适用于衍生类似的干细胞从其他哺乳动物物种。
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 beta (TGF-beta), 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.