Early human trophoblast development has remained elusive due to the inaccessibility of the early conceptus. Non-human primate models recapitulate many features of human development and allow access to early postimplantation stages. Here, we tracked the pre- to postimplantation transition of the trophoblast lineage in superficially implanting marmoset embryos in vivo. We differentiated marmoset naive pluripotent stem cells into trophoblast stem cells (TSCs), which exhibited trophoblast-specific transcriptome, methylome, differentiation potential, and long-term self-renewal. Notably, human TSC culture conditions failed to support marmoset TSC derivation, instead inducing an extraembryonic mesoderm-like fate in marmoset cells. We show that combined MEK, TGF-β/NODAL, and histone deacetylase inhibition stabilizes a periimplantation trophoblast-like identity in marmoset TSCs. By contrast, these conditions differentiated human TSCs toward extravillous trophoblasts. Our work presents a paradigm to harness the evolutionary divergence in implantation strategies to elucidate human trophoblast development and invasion.

中文翻译：

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狨猴和人类滋养层干细胞的信号传导要求不同，并概括了滋养层侵袭的不同模式


由于早期概念的不可及性，早期人类滋养层的发育仍然难以捉摸。非人灵长类动物模型概括了人类发育的许多特征，并允许进入植入后的早期阶段。在这里，我们追踪了在体内浅表植入狨猴胚胎 中滋养层谱系的植入前到植入后过渡。我们将狨猴幼稽多能干细胞分化为滋养层干细胞 （TSCs），其表现出滋养层特异性转录组、甲基化组、分化潜能和长期自我更新。值得注意的是，人类 TSC 培养条件不支持狨猴 TSC 衍生，而是在狨猴细胞中诱导胚外中胚层样命运。我们表明，MEK 、 TGF-β/NODAL 和组蛋白脱乙酰酶抑制联合稳定了狨猴 TSCs 中植入周围滋养层样身份。相比之下，这些条件将人类 TSC 区分为绒毛外滋养层细胞。我们的工作提出了一种范式，可以利用植入策略的进化分歧来阐明人类滋养层的发育和侵袭。