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

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-05-31 DOI:10.1016/j.stem.2024.05.003
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
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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.

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基于原始多能干细胞的模型捕捉到了依赖于 FGF 的人类下胚层细胞系规范
低胚泡是胚泡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。我们在此表明,人类天真多能干细胞(PSC)向低体细胞分化的过程是通过还原到类似于ICM的过渡状态,低体细胞从这种状态中出现,与人类胚泡的分化轨迹一致。我们发现了成纤维细胞生长因子(FGF)信号传导对低分化母细胞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低分化母细胞的形成。在体外,通过限制滋养层外胚层和上胚层的命运,可协同增强对低胚泡的诱导。这一发现修正了之前的报道,并确立了小鼠和人类在系谱规范方面的一致性。总之,这项研究证明了基于人类天真造血干细胞的模型在阐明人类早期胚胎发生机理特征方面的实用性。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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