英国埃克塞特大学Ge Guo小组发现，基于原始多能干细胞的模型捕捉到依赖于FGF的人类下胚层谱系特化。这一研究成果于2024年5月31日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员表明，人类初始多能干细胞（PSC）向下胚层分化的过程是通过还原到类似于ICM的过渡状态，下胚层从这种状态中出现，与人类囊胚的分化轨迹一致。研究人员发现了成纤维细胞生长因子（FGF）信号传导对下胚层分化至关重要的窗口期。重新审视人类胚胎中的成纤维细胞生长因子信号转导发现，在早期囊胚中抑制成纤维细胞生长因子信号转导可抑制下胚层的形成。

在体外，通过限制滋养层外胚层和上胚层的命运，可协同增强对下胚层的诱导。这一发现修正了之前的报道，并确立了小鼠和人类在谱系特化方面的一致性。总之，这项研究证明了基于人类初始PSC的模型在阐明人类早期胚胎发生机理特征方面的实用性。

据悉，下胚层是囊胚内部细胞团中的一个重要胚外组织。利用人类胚胎进行研究具有挑战性。因此，能再现下胚层分化的干细胞模型提供了有价值的替代方案。

附：英文原文

Title: Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification

Author: Anish Dattani, Elena Corujo-Simon, Arthur Radley, Tiam Heydari, Yasaman Taheriabkenar, Francesca Carlisle, Simeng Lin, Corin Liddle, Jonathan Mill, Peter W. Zandstra, Jennifer Nichols, Ge Guo

Issue&Volume: 2024-05-31

Abstract: 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. In vitro, 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.

DOI: 10.1016/j.stem.2024.05.003

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00180-2