源于干细胞的囊胚样结构:研究现状与展望

Blastoids derived from pluripotent cells:Current research status and future prospect

由于样本和伦理的限制,人类早期胚胎发育中仍有许多未完全阐明的问题.而类囊胚的出现使得构建体外模拟胚胎发育,尤其是植入前、植入和早期植入后过程的类器官系统成为可能.但初始方案的类囊胚构建效率较低,且对受精囊胚的模拟还存在较大差异,因此研究人员探索利用不同类型细胞以及不同诱导体系,提高类囊胚的构建效率,并获得了在形态学和转录组水平上更类似于受精囊胚的模型.除了转录组分析,蛋白组和翻译后修饰的组学也被用于探索类囊胚形成的分子机制和与受精囊胚的相似性.同时,类囊胚已经被作为研究模型探索不同基因组特征对胚胎发育的影响以及潜在作用机制.因此,我们总结了近期小鼠和人类的类囊胚模型的研究进展及新型全能样细胞参与构建类囊胚的未来前景.

Due to sample and ethical limitations,many mysteries still exist in the study of early human embryonic development,among which the first lineage specification,the interplay between inner cell mass and trophectoderm and the interaction of uterine endometrium and blastocysts remain to be fully elucidated.The emergence of blastoids makes it possible to obtain models that mimic embryonic development in vitro,especially regarding the preimplantation,implantation and early postimplantation processes.Blastoids are organoid models of blastocysts derived from stem cells that resemble natural blastocysts at the morphological and transcriptomic levels;that is,blastoids comprise an outer layer of trophectoderm-like cells enclosing a cavity and a population of epiblast-like cells and primitive endoderm-like cells.Moreover,blastoids can enable the recapitulation of key events in preimplantation development,such as compaction,polarization,cavitation and cell lineage specification.Moreover,blastoids also partially exhibit postimplantation potential in vivo and in vitro.However,the efficiency of the blastoid induction system has been relatively low,and there are some defects in blastoid modelling blastocysts,which has inspired researchers to improve these systems.To date,various mouse and human blastoids using different cell types and induction systems have been developed.The blastoid induction efficiency has significantly increased,and these blastoids are more similar to natural blastocysts at the morphological and transcriptomic levels.In addition to transcriptomic analysis,proteomic and posttranslational modification analyses have also been used to explore the molecular mechanisms underlying blastoid formation and their similarities and differences to natural blastocysts.Moreover,human parthenogenic embryonic stem cells have been employed to generate parthenogenic blastoids and detect the impacts of parental genomes and genome imprinting on human embryonic development.In addition to pluripotent stem cells,totipotent-like cells have been proposed as preferred cell resources to construct blastoids for their greater developmental potential.In recent years,many kinds of mouse and human stable totipotent-like cells have been generated that have shown totipotent features and exhibited greater developmental potential.Moreover,some attempts to generate blastoids using totipotent-like cells have been made,and such blastoids have shown typical blastocyst features.In addition,great progress has also been made in research on primate blastoids,which will augment the knowledge regarding human embryonic development.Here,we summarize recent advances in the blastoid research field and discuss future prospects for the involvement of novel totipotent-like cells in blastoid formation.These findings have shown that blastoids have important research and application potential in the elucidation of early embryo development mechanisms,the illumination of peri-implantation embryo development events,the screening of new drug molecules for reproductive diseases and the assessment of the reproductive toxicity of new drugs.However,there are still some unresolved issues and challenges in the development of blastoids that are also discussed in this review.