关键词: 早期胚胎发育, 干细胞, 非整合型胚胎模型, 整合型胚胎模型, 着床前, 着床后

Abstract:

THuman early embryonic development is critical for a healthy fetus birth. However, the specific molecular regulatory mechanisms of lineage development, cell fate decisions and embryonic patterning are still shrouded in mystery. Our knowledge about early human embryogenesis has been greatly improved with the recent progress in in vitro culture conditions for human blastocysts and the advancements in omics technology. However, ethical and technological challenges continue to pose obstacles in these studies. With the rapid development of human pluripotent stem cells, they can be coaxed to form embryo-like structures that mimic early human embryonic development in vitro, termed "embryo models". Interest in human embryonic development has been reinvigorated with the continuing advances in this area. Human embryo models can be divided into two categories "non-integrated embryo models" and "integrated embryo models" according to the different cellular components they possessed. Integrated embryo models represent the embryo-like structures containing both embryonic and extra-embryonic cell types, including blastoids, human extra-embryoids (hEEs), E-assembloids, stem-cell-derived synthetic whole embryo models (SEMs), peri-gastruloids, bilaminiods and heX-embryoids. While non-integrated embryo models sometimes lack the extra-embryonic tissues, including embryoid bodies (EBs), gastruloids, micro-patterned colonies, post-implantation amniotic sac embryoids (PASE). Besides, non-human primate cynomolgus monkey models have greatly expanded our knowledge towards human developmental biology. In this review, we summarized recent human stem cell-based non-integrated and integrated embryo models, and pointed out the technical challenges remained with proposed future directions. These findings lay an important foundation for understanding early human embryonic development, promoting research into human stem cells and their application, as well as preventing and treating early pregnancy loss or congenital diseases. On the other hand, embryo-like structures derived from human stem cell-based integrated embryo models, although do not fully, almost recapitulate the key events and structural organization of the in vivo counterparts, thus eliciting a serious compact on traditional ethical and practical concerns. In the future, non-integrated human embryo models and non-human primate models, which pose fewer ethical challenges, may provide a straight forward way to study the human early embryonic development.

Key words: early human embryonic development, stem cell, non-integrated embryo model, integrated embryo model, pre-implantation, post-implantation