Chinese scientists worldwide the world's first realization of mammals' complete chromosomes to open up new fields of mammalian chromosomal editing

Author:Guangming Daily client Time:2022.08.26

On August 26, the international academic journal "Science" published a pioneering achievement of Chinese scientists -Researcher Li Wei and Zhou Qi Researcher Team of the Institute of Animal Research of the Chinese Academy of Sciences and Beijing Institute of Stem cells and Researchers in Beijing. The comprehensive chromosomal connection of mammals, and creates a mouse with a new nuclear (chromosome group).

Some comments believe that this work means that the biological engineering technology breakthroughs again, and in order to deeply understand the molecular mechanism of the large -scale reconstruction of mammals chromosomes, such as the large -scale reconstruction of mammals chromosomes. "The synthetic biological research strategy has laid the corresponding technical platform.

Breaking through the technical bottleneck of dyeing weight row research, the complete dyed weight row of mammals for the first time

To understand this achievement, we must first understand a concept -chromosomal rearrantement. Li Wei introduced that the chromosome weight row refers to the break of chromosomes and connects with other chromosomes to form a new chromosomal.

In the long process of biological evolution, the dyeing weight row is an important factor that causes quality changes and leaps. But for individuals, dyeing weight is more of the disease -some types of children with leukemia and infertility of children are caused by dyeing weight.

To understand the mystery of color dyeing weight, it can further reveal the mystery of human evolution, and it can also make a leap in the treatment of various diseases. Therefore, dyeing weight is the focus area of ​​biologists. In recent years, the precise re -arrangement of chromosomes has been the first to be successful on genomic composition and a polarized yeast. However, because mammalian genome is much more complicated than yeast genome, the overrun of complete chromosomes on mammals has not been successfully achieved.

After years of hard work, Chinese scientists have first achieved the complete dyeing weight of mammals worldwide in the world, and have achieved new breakthroughs in synthetic biology. "Our research breaks the technical bottleneck, and uses mouse gangbang embryo stem cells and CRISPR gene editing tools to successfully connect the longest chromosomes No. 1 and 2, and the medium -length 5 and 4 chromosome Perform the first and tail connection, and it is also found that chromosome breaks and re -connection may occur during chromosomal connection. "Li Wei said:" The results of the study showed that two independent chromosomes from mice can be used as non -homologous after gene editing. The end connection repair method is connected to a chromosome. "

"Create" mice with a new and unique chromosome group, will have a huge impact on understanding evolution, design life, and disease treatment

On this basis, the researchers further studied the impact of a specific dyeing weight connection.

First of all, researchers have confirmed that the chromosomes of mammalian cells are not longer and better, which will cause abnormal cell division. Li Wei introduced that at the level of the cell surface, the multi -energy gene expression and differentiation of stem cells after chromosomal connection have not changed significantly, and the longest chromosomal connection (number 2 and No. 1 chromosome connection) doubles The rate ofization has been significantly accelerated, and spontaneous multiplication will still be spontaneous. "This phenomenon is caused by abnormal cell division due to the long length of chromosomes, which also proves that the length of the chromosomes of mammalian cells has a certain limit. For mouse cells, the upper limit of the chromosome length is between 308.3MB and 377.6MB. "

Secondly, scientific researchers "created" mice with a new and unique chromosome group. According to Li Wei, in order to solve the impact of specific chromosome weight on the animal surface type, researchers successfully obtained the mice connected to the chromosomal connection by the polymeter stem cells -it seems to be with ordinary mice It is no different, but in fact, there is no world, a new and unique chromosome group.

Studies have found that different chromosomal connections have different effects on mice. The longest of the longest chromosomal connection (No. 2 and No. 1 chromosomal connection) makes the embryo development cannot be carried out normally. The break is re -connected to the 17th chromosomes, and the generated mice showed the abnormal growth curve and behavior. Mice No. 4 and No. 5 chromosome did not show obvious abnormalities.

At the same time, the connected chromosomes can be passed to the offspring, and further mating can produce pure mice. Li Wei said: "This proves that the connection of the two chromosomes will not cause absolute reproductive isolation. However, the genital force of mice carrying chromosomes with chromosomes has dropped significantly. Further exploration and discovery. The homologous chromosomes are performed normally, but the separation of homologous chromosomes after the federation will occur abnormal. "

Finally, the researchers also comprehensively analyzed the trend of chromosomal space structures in embryonic stem cells, neuroplastic stem cells, and brain. Studies found that with differentiation, changes in the spatial structure of chromosomes weakened with differentiation.

Li Wei said that this study strictly complies with my country's laws and regulations and relevant state regulations, and complies with my country's and international ethical norms. "Our research first established new technologies for mammalia's complete chromosomal programming connection, and realized the editors of ultra -large -scale genomes, adding new research tools to mammalian synthetic biology. Mammalian synthetic biology for chromosomal design synthesis provides an important reference; through re -constructing chromosome weight emission events in the laboratory mouse model, it helps understand the evolutionary chromosomal fusion, which also proves the correlation between the chromosomal weight and reproductive isolation. It provides new ideas for evolutionary biology research. The precise re -exclusion technology of chromosomes in order to establish an animal model of dyeing and weight discharge diseases, and study the pathogenesis of infertility and tumors caused by dyeing weight. Provides new technical means. " The mouse seems to be no different from ordinary mice, but in fact, there is no world that has never existed, and the new and unique chromosome group. The picture is provided by the Institute of Animal Research, Chinese Academy of Sciences

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