动物实验,胚胎 z-bo 2020-09-02 376

　　In a new study, researchers from the University of Cambridge and the University of Nottingham in the United Kingdom demonstrated how pig embryos and human embryonic cells exhibit significant similarities in their early developmental stages. By combining these two models, they hope to improve people's understanding of the origin of diseases such as pediatric germ cell tumors and fetal malformations. The relevant research results were published online in Nature on June 7, 2017, and the title of the paper is "Principles of early human development and germ cell program from conserved model systems".

　　As the precursor cells of eggs and sperm, primordial germ cells are one of the earliest cells that appear in a human embryo after implantation, appearing at about 17 days, while surrounding cells continue to form the rest of the human body. However, little is known about how they originated. Currently, the law prohibits the cultivation of human embryos older than 14 days, which prevents the study of events such as the production of primordial germ cells and subsequent gastrulation.

　　Now, scientists use a combination of human and pig developmental models to clarify these events. They confirmed for the first time that the interaction between two key genes is essential for the formation of these primordial germ cells, and this "gene combination" is not the same in all species.

　　First, by using human pluripotent embryonic stem cells in vitro, Professor Azim Surani of the Wellcome Foundation/Gerdon Institute of Cambridge University and his colleagues established a method that simulates the genetic and cellular changes that occur during the development to gastrulation. model. Human pluripotent embryonic stem cells are "master cells" found in embryos and have the potential to become almost any cell type in the human body.

　　Given that these stem cells can proliferate and can be accurately genetically manipulated, this model system provides a powerful tool to detail how human cells transform into different cell types during early development and what changes may cause human diseases. Molecular analysis.

　　This study confirmed that when the embryo develops to gastrulation, the cells temporarily acquire the potential to form primordial germ cells, but shortly thereafter, they lose this potential. Instead, they obtain precursor cells that form blood cells and muscle cells (mesoderm cells). ) Or the potential of intestinal cells, lung cells and pancreatic cell precursor cells (endoderm cells). This model also revealed that although the genes SOX17 and BLIMP1 are critical to the fate of germ cells, SOX17 then plays another role in the production of endoderm tissue.

　　However, in order to accurately describe how the embryo develops, it is necessary to understand how the cells behave in the three-dimensional environment of a normal embryo. This cannot be achieved by studying the most commonly used mouse embryos. Mouse embryos develop from cylindrical eggs, while human embryos have a flat disk shape. On the other hand, pig embryos can be easily obtained, which develop into a flat disc shape similar to human embryos, and are ethically more acceptable than studying non-human primate (monkey) embryos.

　　Researchers from the University of Nottingham carefully analyzed the complete planar disc structure of pig embryos at different developmental stages, and found that the development of these embryos was observed in an in vitro human embryo model and in vitro non-human primates Embryonic stem cells match. For example, as predicted from the human embryo model, porcine germ cells appear during gastrulation and express the same key genes in human germ cells. Both human germ cells and pig germ cells also exhibit key features of this cell lineage, including initiating reprogramming and resetting the epigenome, and developing as germ cells to produce eggs and sperm.

　　The human embryo model and pig embryo model used to study early development and cell fate determination may reflect the key events that occur in the human early embryo in the uterus. All in all, the knowledge gained using this method can be applied to regenerative medicine: to obtain relevant human cell types, which may be used to help understand and treat human diseases, and to understand how mutations that disrupt early development can lead to human diseases.

　　Dr. Ramiro Alberio from the School of Biological Sciences at the University of Nottingham said, “We have shown how egg and sperm precursor cells are produced in pigs and humans. Pigs and humans have similar embryonic development patterns. This suggests that pigs can be used to study early human embryos. A perfect model system to develop and improve our understanding of the origin of genetic diseases."

　　Dr. Toshihiro Kobayashi, a researcher in the Surani Laboratory of the Gordon Institute, added, “We are currently not allowed to study human embryo development for more than 14 days, which means that certain key stages in our development are still a mystery. The development of humans and pigs is still a mystery. The significant similarity between the two suggests that we may soon be able to reveal the answers to some of our long unanswered questions."