人胚胎早期发育与干细胞

Early human embryo development and stem cells

人胚胎早期发育包括三个重要阶段:①从受精卵到晚期囊胚的着床前阶段;②从晚期囊胚到原肠运动前的围着床阶段;③从原肠运动到早期器官发生的原肠后阶段。后两个阶段统称为着床后早期发育阶段。妊娠过程中,不育(胚胎着床失败或流产)和胎儿出生缺陷,很大程度上是胚胎的着床后早期发育出现异常所致。人着床后早期胚胎,由于位于母体子宫,且尺寸较小,不易对其观察和研究,因此,这一阶段的胚胎发育过程长期处于“黑匣子”状态。近年来,随着单细胞组学技术和胚胎体外延长培养系统的建立,以及胚胎和胚外干细胞、类器官和类胚胎领域的快速发展,使得人胚胎着床后早期发育的神秘面纱被慢慢揭开。本文从人胚胎早期发育、胚胎和胚外干细胞、类胚胎和类器官研究的视角,结合细胞通信、谱系互作、信号梯度、黏附分子、生物力学和细胞外基质等因素对细胞分选、迁移重排和自我组织的影响,概述了人胚胎早期发育过程中的发育原理,当前胚胎和胚外干细胞的研究进展以及用其模拟人胚胎早期发育的研究现状、存在问题和发展方向,以期能够帮助理解人胚胎早期发育的奥秘。

The early development of the human embryo includes three important stages:①the pre-implantation stage from the zygote to the late blastocyst;②the peri-implantation stage from late blastocyst to pre-gastrulation embryo;and③the most mysterious post-gastrulation stage from gastrulation to early organogenesis.The latter two stages are collectively referred to as the early post-implantation developmental stage.During pregnancy,infertility(implantation failure or miscarriage)and birth defects of the fetus are largely due to abnormalities in human early postimplantation development.Human early postimplantation embryo,due to its small size and location in the mother’s uterus,is difficult to observe and study.Therefore,the embryonic development process at this stage has been in a black box state for a long time.In recent years,with the emergence of single-cell omics technology and extended in vitro culture system of human blastocysts,as well as the rapid development in the fields of embryonic and extraembryonic stem cells,organoids and embryoids,the mystery of the human early postimplantation development is gradually being lifted.In order to help understand the mysteries of early human embryonic development,this review primarily introduces the lineage diversification,key developmental events and known developmental principles during early human embryogenesis;summarizes recent progress in the research on human embryonic and extraembryonic stem cells(including totipotent stem cells,embryonic stem cells,trophoblast stem cells,primitive endoderm stem cells and extraembryonic mesoderm cells);presents the effects of cell communication,lineage interaction,signal gradient,adhesion molecules,biomechanics,and extracellular matrix on cell sorting,migration rearrangement and self organization in embryoids and organoids;reviews the current research status of human early post-implantation embryogenesis,stem cell-based embryo models and organoids;and finally proposes the prospects and possible solutions to the problems and challenges existing in the research of human early post-implantation development using stem cell-derived embryo models or organoids.