Generation of human blastocyst-like structures from pluripotent stem cells
Yong Fan, Zheying Min, Samhan Alsolami, Zhenglai Ma, Enbo Zhang, Wei Chen, Ke Zhong, Wendi Pei, Xiangjin Kang, Pu-Yao Zhang, Yongliang Wang, Yingying Zhang, Linfeng Zhan, Haiying Zhu, Chenrui An, Rong Li, Jie Qiao, Tao Tan, Mo Li, Yang Yu
Abstract
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.