Generation of human blastocyst-like structures from pluripotent stem cells.

Generation of human blastocyst-like structures from pluripotent stem cells.
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从多能干细胞生成人类囊胚样结构

DOI:
10.1038/s41421-021-00316-8
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发表时间:
2021-09-07
期刊:
影响因子:
33.5
通讯作者:
Yu Y
Yu Y
中科院分区:
生物学1区
文献类型:
--
作者:
Fan Y;Min Z;Alsolami S;Ma Z;Zhang E;Chen W;Zhong K;Pei W;Kang X;Zhang P;Wang Y;Zhang Y;Zhan L;Zhu H;An C;Li R;Qiao J;Tan T;Li M;Yu Y

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人类囊胚由胚胎的前三个细胞谱系组成:滋养外胚层、上胚层和原始内胚层,所有这些对于早期发育和器官形成都至关重要。然而,由于伦理问题和人类囊胚的限制,对早期人类胚胎发生的全面了解仍然缺乏。为了弥合这一知识差距,需要一个可靠的模型系统,重现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,用于从人扩展多能干细胞(EPS)中产生胚泡样结构(EPS-胚状体)。形态学和单细胞转录组学分析显示,EPS-胚状体包含关键细胞谱系,并且在转录上与人类胚泡相似。此外,在胚胎结构、细胞谱系和转录谱方面,EPS-类胚体与体外培养8或10天的人胚胎相似。总之,我们开发了一个可扩展的系统来模拟人类囊胚发育,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 comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.
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