The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in the blastocyst. Research with human embryos is challenging. Thus, stem cell models that reproduce hypoblast differentiation provide valuable alternatives. We show here that human naive pluripotent stem cell (PSC) to hypoblast differentiation proceeds via reversion to a transitional ICM-like state from which the hypoblast emerges in concordance with the trajectory in human blastocysts. We identified a window when fibroblast growth factor (FGF) signaling is critical for hypoblast specification. Revisiting FGF signaling in human embryos revealed that inhibition in the early blastocyst suppresses hypoblast formation. , the induction of hypoblast is synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports and establishes a conservation in lineage specification between mice and humans. Overall, this study demonstrates the utility of human naive PSC-based models in elucidating the mechanistic features of early human embryogenesis.

中文翻译：

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基于幼稚多能干细胞的模型捕获 FGF 依赖性人类下胚层谱系规范


下胚层是位于囊胚内细胞团内的重要胚胎外组织。人类胚胎研究具有挑战性。因此，再现下胚层分化的干细胞模型提供了有价值的替代方案。我们在此表明​​，人类幼稚多能干细胞（PSC）向下胚层的分化是通过恢复到类似 ICM 的过渡状态而进行的，从该状态开始，下胚层的出现与人类囊胚的轨迹一致。我们确定了成纤维细胞生长因子 (FGF) 信号传导对于下胚层规范至关重要的窗口期。重新审视人类胚胎中的 FGF 信号传导表明，早期囊胚中的抑制会抑制下胚层的形成。 ，通过限制滋养外胚层和外胚层的命运来协同增强下胚层的诱导。这一发现修正了之前的报告，并建立了小鼠和人类之间谱系规范的保守性。总体而言，这项研究证明了基于人类原始 PSC 的模型在阐明早期人类胚胎发生的机制特征方面的效用。