Cells capable of everything
Regeneration, cloning – the search for alternative ways to create or restore living tissues is one of the most important goals of biologists. Shen Ding and his colleagues from the Tsinghua University School of Pharmaceutical Sciences have published an innovative paper on this issue in the journal Nature. They identified a mixture of substances that returns stem cells to the state of totipotent, and can also maintain the potential of the resulting cells.
In nature, a zygote is formed as a result of the fusion of a sperm and an egg. This event triggers a process in which the zygote divides, forming new cells that continue to divide and become more differentiated.
As specificity is acquired, the differentiation potential is lost. Cells at the stages of a unicellular and bicellular embryo are called totipotent stem cells. They give rise to pluripotent and multipotent stem cells. Usually, after totipotent cells, none of the other stem cells have the ability to give life on their own.
In order to better study and control totipotent stem cells, Ding and colleagues created a system that ensures the induction and preservation of the functionality of these cells, and confirmed their identity using strict criteria.
To do this, the group selected and tested thousands of combinations of small molecules. After conducting several stages of analysis, they identified three of them (TTNPB, 1-Azakenpaullone and WS6), which together can transform pluripotent stem cells of mice into cells with totipotent characteristics – chemically induced totipotent stem cells (ciTotiSCs).
The researchers then studied in detail both the totipotency and the absence of pluripotency of cells treated with a mixture of TTNPB, 1-Azakenpaullone and WS6 (a mixture of TAW). These cells have passed strict molecular testing criteria at all levels of the transcriptome, epigenome and metabolome. For example, the team found that TAW includes hundreds of important genes in ciTotiSCs. These genes are usually found in totipotent cells and have been identified by other researchers as a criterion for assessing totipotence. At the same time, the genes associated with pluripotent cells were suppressed by a mixture of TAW in ciTotiSCs.
To confirm that the resulting cells have a true totipotent state, the researchers tested their ability to differentiate in vitro, and also injected them into a mouse embryo to evaluate differentiation in vivo. They found that ciTotiSCs behaved as truly totipotent not only in vitro, but also differentiated into both embryonic and extraembryonic lines in vivo. This is a typical characteristic of normal totipotent cells, which can potentially develop into both a fetus and a yolk sac and placenta, whereas pluripotent cells can only develop into a fetus.
In addition, when the researchers used special conditions for the cultivation of ciTotiSCs, subsequent cells also showed similar signs of totipotence. This observation suggests that the totipotency of TAW-induced cells can be maintained under laboratory conditions, and thus a stable system is established.
Such a system will make it possible to carry out many scientific studies concerning the origin of life. For example, scientists will be able to manipulate totipotent cells to better understand the highly organized process at the very beginning of life. Moreover, a deep understanding and, consequently, management of totipotent cells will have a wide range of consequences, up to the acceleration of the evolution of the species.
The authors acknowledge that many of these possibilities will cause ethical disputes in society.
Article Y.Hu et al. Induction of mouse totipotent stem cells by a defined chemical cocktail is published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Tsinghua University: Scientists take the first step to master an all-powerful cell type in the beginning of life