Open the possibility of restoring a new life!Tsinghua University team first discovered the “magic potion” of totipotent stem cell transformation – Programmer Sought

IT House reported on June 23, according to the public account of Tsinghua University, Ding Sheng’s team from the School of Pharmacy of Tsinghua University took mammals and mice as the main research objects.For the first time, the “magic potion” of directed induction of totipotent stem cells in vitro and their stable culture was discovered. In the future, not only the hairs on Sun Wukong’s body in the novel,Any somatic cells in animals, such as blood and skin, can be reprogrammed into pluripotent stem cells, and then “medicine” to become totipotent stem cells that can independently form life. On June 21, the research results of Ding Sheng’s team – “Induction of Totipotent Stem Cells in Mice Using Small Molecule Cocktail Combination” were published in the top international academic journal “Nature”. The research marks the transition from cloning technology to regenerative medicine,In the field of life sciences, other avenues than natural embryonic gestation are opened to create or restore the possibility of new life.

With the scientific imagination of a mouse jumping out of the incubator, Ding Sheng’s team focused on three aspects: without the participation of germ cells, and solving the conditions under which pluripotent stem cells can be reversed into individuals with independent production of life The competent totipotent stem cells and the reversed totipotent stem cells can be stably cultured and self-replicating. “Reversal has two meanings. On the surface, it seems to be the ‘rejuvenation’ of cell age, but it is essentially the turning of the cell’s ‘fate’, that is, whether it can return to the stage of totipotent stem cells, so as to have the potential to produce independent living individuals.” Speaking of this This breakthrough in research, Professor Ding Sheng did not talk much, but he hit the nail on the head.

In mammals, totipotency refers to the ability of a cell or class of cells to develop into all differentiated cells of intraembryonic and extraembryonic tissues, and thereby to form an organism. Taking mice as an example, only fertilized eggs and two-cell stage blastomeres are truly totipotent. So far, the production of mammalian life can only rely on germ cells, which are produced through sperm-egg combination and cloning techniques. Ding Sheng’s team’s research does not require the participation of germ cells, and can reverse any somatic cell in a mouse to a stage similar to that of a two-cell embryo.

In this reversal process, stem cells that will “72 change” are indispensable. According to the developmental grade and differentiation ability of stem cells,From high to low, it can be divided into totipotent stem cells, pluripotent stem cells and unipotent stem cells. Totipotent stem cells can eventually develop into complete individuals and extraembryonic tissues, such as fertilized eggs and two-cell stage embryos; pluripotent stem cells have unlimited proliferation and multi-directional differentiation potential, such as embryonic stem cells; unipotent stem cells, only have the ability to differentiate into a limited number of closely related cell types, such as hematopoietic stem cells.

Since 2015, Ding Sheng has led a team in his laboratory to find a “magic potion combination” for reversing mouse pluripotent stem cells to totipotent stem cells based on his more than 20 years of research experience in regulating stem cells through compounds. To better study and control pluripotent stem cells, he said, the team built a system that could induce and maintain these cells, and used strict criteria to confirm pluripotent stem cell identity.

Use mature technology to reverse from somatic cells to pluripotent stem cells, then find suitable small chemical molecules, and combine them into a “magic potion” according to a certain logic to induce pluripotent stem cells. In just a few days, totipotent stem cells can be generated and stabilized nourish.

In 2020,Ding Sheng led the team to discover that a combination of three small chemical molecules can induce mouse pluripotent stem cells into cells with totipotent properties. Because the combination of three small chemical molecules is similar to the preparation of cocktails, we call this molecular combination “TAW cocktail drug combination”.

After verification, the team found that after adding the “magic potion” induced cells, hundreds of key genes were turned on. These genes are commonly found in totipotent stem cells and have been identified by other researchers in the field as criteria for determining totipotency. Meanwhile, genes associated with pluripotent stem cells were silenced. The team also tested the differentiation potential of TAW-induced cells in vitro and injected them into early mouse embryos to observe their differentiation potential in vivo. They found that these cells not only exhibited the characteristics of true totipotent stem cells in a dish, but also differentiated into intra- and extra-embryonic lineages in vivo, with the potential to develop into a fetus, a yolk sac, and a placenta.

In addition, as very fickle stem cells, mouse totipotent stem cells are transient and irreversible in their natural state, and will rapidly divide, differentiate, and develop. One of the important functions of the “TAW cocktail drug combination” is to “capture” totipotent stem cells so that they can self-replicate in vitro while maintaining their totipotent state.

Although the scientific imagination of popping a mouse out of an incubator has not yet been fully realized, the pioneering research on totipotent stem cells by Ding Sheng’s team has opened a door to recreate individual life and even accelerate the evolutionary creation of different species possible.