从多能性干细胞中培养出人的囊胚样结构

人类胚泡由胚胎的前三个细胞系组成：滋养外胚层、外胚层和原始内胚层，所有这些都对早期发育和器官形成至关重要。然而，由于伦理问题和对人类胚泡的限制，对早期人类胚胎发生仍缺乏全面的了解。为了弥补这一知识差距，需要一个可靠的模型系统来概括人类胚胎发生的早期阶段。在这里，我们开发了一种三维（3D）、两步诱导方案，用于从人类扩展多能干细胞（EPS）产生胚泡样结构（EPS卵裂球）。形态学和单细胞转录组学分析表明，EPS胚泡含有关键的细胞谱系，在转录上与人类胚泡相似。此外，在胚胎结构、细胞谱系和转录组学特征方面，EPS卵裂球与体外培养8或10天的人类胚胎相似。总之，我们开发了一个可扩展的系统来模拟人类胚泡的发育，这可能有助于研究早期发育缺陷导致的早期植入失败。

Human blastocysts are composed of the three earliest cell lineages of the embryo: trophectoderm, epiblast, and primitive endoderm, all of which are critical for early development and organogenesis. However, due to ethical concerns and restrictions on human blastocysts, our comprehensive understanding of early human embryogenesis remains incomplete. To address this knowledge gap, a robust model system that can recapitulate the early stages of human embryogenesis is needed. Here, we developed a three-dimensional (3D), two-step induction protocol to generate blastocyst-like structures (EPS blastoids) from human expanded pluripotent stem cells (EPSCs). Morphological and single-cell transcriptomic analyses revealed that EPS blastoids contain key cell lineages that are transcriptionally similar to human blastocysts. Furthermore, EPS blastoids resemble human embryos cultured in vitro for 8 or 10 days in terms of embryonic structure, cell lineages, and transcriptomic profiles. Collectively, we developed a scalable system to model human blastocyst development, which may facilitate research on early implantation failure caused by early developmental defects.