Institute of Zoology, Chinese Academy of Sciences: Rat mice "catch out" new stem cells

Institute of Zoology, Chinese Academy of Sciences: Rat mice "catch out" new stem cells

January 26, 2016 Source: Bio Valley

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Occasionally, there are hybrids between different species in nature, including the zebras (zebras and horses), the Pefolo cattle (bison and beef cattle), and the well-known scorpions (scorpions and horses), while the hybrid rice in the plant world is people. The most familiar example. The important role of this sputum relationship is not in the production of offspring, but in the use of the advantages of hybridization to produce a third and completely different breed. However, in the natural state, there are many unfavorable factors in the hybridization behavior of wild animals. Even if some members of different species mate successfully, their offspring usually cannot survive due to genetic differences between species or carrying different numbers of chromosomes. Or can't have children.

Can we do the interspecific hybridization in nature in the laboratory? Even to complete the cross between distant relatives that are unlikely to occur in nature?

Scientists have created hybrid cells between a variety of distant relatives, such as mouse-rat, human-rodent, human-bovine hybrid cells. However, since these cells are produced by somatic cell fusion, they are all tetraploid and the genome is unstable, and a large number of chromosome losses often occur, and there is almost no differentiation ability. The "evolution" in such dishes seems to have entered a dead end.

That's right, it seems that scientists always rack their brains to make a breakthrough. Academician Zhou Qi of the Institute of Zoology, Chinese Academy of Sciences has opened up a new path to create a new type of stem cell, a heterozygous diploid embryonic stem cell. This result is the first artificially created heterozygous embryonic stem cells in stable diploid form, which consists of a set of rat and mouse genomes, and the heterologous genome is stable in diploid form.

To produce such stem cells, it is first necessary to establish haploid embryonic stem cells of mammals of different species. They selected rats and mice as subjects. Zhou Qi's research team has made breakthroughs in the research of rat and mouse solitary (female) haploid stem cells. The solitary male haploid stem cells are injected into the oocytes from which the nucleus has been removed, and are developed and cultured in vitro, while the parthenogenetic haploid stem cells are injected into the sperm cells from which the nucleus is removed. obtain. This haploid stem cell obtained by a similar clone has only half of the chromosomes of normal cells (we call it haploid) and is capable of stable passage. At the same time, haploid embryonic stem cells can not only expand and multiply like ordinary stem cells, but also replace sperm or eggs as germ cell breeding offspring.

Based on the above studies, the researchers obtained the heterozygous diploid embryonic stem cells by fusing mouse solitary (female) and rat parthenogenetic (male) haploid stem cells by cell fusion technique. The original mouse germ cells have 20 chromosomes, while the rat is 21 chromosomes, and the sperm eggs cannot develop after fusion. The heterozygous diploid embryonic stem cells have the ability of embryonic stem cells to differentiate into three germ layers, and even differentiate into early germ cells, and maintain the stability of the heterologous diploid genome during culture and differentiation.

"It can differentiate into a variety of heterozygous cell populations and form tissues. Next we hope to get organs for the development of hybrid cells," said Li Wei, a researcher who participated in the study.

Although the organ has not yet formed, it sounds very cool.

In addition to breaking people's understanding of conventional heterogeneous heterozygosity, such an "unbelievable" cell has become a "tool" for scientific research. After gene expression analysis, heterozygous diploid embryonic stem cells exhibit unique gene expression patterns and unique biological traits. Scientists have compared hybrid cells to jade jade, which has both mouse and mouse genomes. Biological characteristics, the analysis of the combination of the two can effectively unearth the molecular regulation mechanism of the differences between species.

"Heterogeneous hybrid cells combine the genetic material and traits of two species, allowing us to explore the molecular basis of the different shapes between species." Li Wei considers this a very unique tool - for evolutionary biology, developmental biology And research such as genetics provides new models and tools.

Hybrid cells also have a peculiar phenomenon. Its X-chromosome inactivation does not use the "random inactivation" pattern common in mammals, but uses the mouse X chromosome-specific inactivation mode.

Project participant Li Xin said: "This is a very unique phenomenon that has never been reported. Using this characteristic of hybrid cells, we systematically identified the mouse X chromosome inactivation escape gene, revealing the X chromosome loss. New ways and new mechanisms for living and inactivating escapes."

In the future, these heterologous diploid hybrid stem cells with embryonic stem cell characteristics will put the characteristics of different species in the laboratory culture dish, which will help scientists to complete more new biological discoveries.

Naturally occurring reproductive isolation has so far been an unbreakable rule in the evolution of species, especially the higher the barriers between animals. Whether we can break through this isolation and even make breakthroughs in higher animals such as primates, we will wait and see.

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