"Black box" opens around bed-period embryo development

The development of human embryos begins with the binding of the fine eggs, and the fertilized eggs develop through multiple fissures, which are formed by the cysts of the inner cell cluster and the nourishing layer of cellsHuman blastocyst bed generally occurs on the 5th to 7th day after fertilization, the embryo and the endometrial adhesion and gradually invade, in order to continue to develop to form a fetusIn the case of natural pregnancy, there is a 20% or more probability of discontinuation or miscarriageThe success rate of assisted reproductive technology is about 40%, and even after pre-implantation genetic testing, selecting a normal lysomal embryo for transplant, about half of the embryos will still fail in bed or miscarry earlyThe most important reason for these problems is the abnormal development of early embryosPrevious studies of bed processes are usually conducted using patterned organisms such as miceUnder the internationally recognized 14-day principle, research into human embryos is allowed to reach 14 days after fertilizationHowever, due to technical limitations, it is difficult to obtain early after bed (fertilized 7 days to 14 days) of human embryos, the human development process around the bed is still a "black box."this study simulates the bed and early post-bed development of human embryos using human embryo culture techniques, and systematically analyzes the genetic expression and epigenetic characteristics that regulate the differentiation of embryonic cell lineage at this critical stagestudies have found that human embryos gradually have the ability to reconstruct themselves and bed in vitro in the late stage of the blastocystThe embryo around the bed includes 3 main cell lineages, namely the upper embryo layer, the original endoblast layer and the nourishing outer embryo layer, each spectrum gradually presents its own unique gene expression characteristics, such as the upper embryo layer shows a clear polysital transformation, the original endoblast layer gradually expresses the genes associated with the development of the egg cystic, and the bed-related nourishing outer embryo cells are specifically characterized to become the metagencent nourishment layer and the cell nourishing layerThe study also found new combination nourishing layer cell marker genes, such as TCL6 and TBX3New lineage marker genes facilitate genealogy identification in early embryos and facilitate stem/progenitor cell derivation researchstudy also found that the X chromosome inactivation and upward adjustment in the bed-in-form embryos coexisted to regulate the dose of gene expression on the X chromosomeFemale embryos gradually show a phase of random inactivation (XCI) of the parent or parent X chromosome, but the dose of x chromosome has not yet been balanced in female and male embryos, which have developed to 12 days, and on the other hand, the expression of x chromosome genes should be balanced with the dose of the autosomal chromosome, which needs to be achieved by raising the X chromosome (XCU) in the female or maleX chromosomes active in late embryonic single cells need to be increased to twice the expression dose to reach the same expression dose as two copies of the normal chromosome (The expression ratio of X chromosomes/normal chromosomes is increased from 1:2 to 2:2)In bed time, both female and male embryonic cells initiate X chromosome upwards, but have not yet reached twice the level of upward adjustment in addition, , the team conducted an in-depth analysis of DNA methylation in three major cell lineages using their own single-cell multigroup sequencing techniques The results showed that the three main cell lineages had similar DNA methylation patterns in front of the bed, i.e the stage of blastocyst development, and after bed, re-methylation took place and their unique DNA methylation characteristics were quickly obtained The results show that the embryo underwent epigenetic reprogramming during bedtime, and DNA methylation was involved in the fate of the cell this study is of great value for understanding the early embryonic development and bed mechanism of human beings, exploring the causes of bed failure, and providing a new theoretical basis for the diagnosis and treatment of difficult cases such as clinical early abortion and fetal malformation Although the specific differences between human and in vitro embryo development need to be further studied, this study provides an important basis for optimizing the in vitro bed system and for the study of the differentiation of pluripotent stem cells and embryo development Zhou Fan, a postdoctoral fellow at Peking University, and Dr Wang Rui, Yuan Peng, Ren Yi, and Mao Yuno are the first authors of the thesis, and Tang Fuyuan and Qiao Jie are the co-authors of the thesis The study was supported by the Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China and the National Key Research and Development Program.