Researchers at Tsinghua University in China have developed a new drug cocktail that can convert cells into totipotent stem cells, the very seeds of life. These cells can differentiate into any cell in the body, potentially bypassing the need for sperm and eggs to grow an organism.
Not all stem cells are created equal – they sit in a branching hierarchy of differentiation potential. Multipotent stem cells are found in many tissues in adults, where they can turn into a few types of cells associated with that tissue or organ to help healing. A step earlier in the development tree are pluripotent stem cells, which are found in embryos and can become almost any type of cell in the body.
But at the top of the chain sit what are known as totipotent stem cells, which can become any cell in the body as well as supportive tissues like the placenta. These mark the very beginning of development, including the first single cell that forms from a fertilized egg, and they persist for the first few stages of development. After that, the cells differentiate into pluripotent stem cells and further specialize into all the cells of the body as it develops.
In recent years scientists have been able to take adult cells and induce a pluripotent state in them, which forms the basis of research into stem cell regenerative medicine. But in the new study, the Tsinghua team took things a step further, returning pluripotent stem cells to a totipotent state for the first time.
The researchers started by screening thousands of combinations of small molecules, until they identified a particular mix of three that seemed to induce totipotency in pluripotent stem cells from mice. They named their concoction the TAW cocktail, after the three molecules in it – TTNPB, 1-Azakenpaullone, and WS6.
Molecular testing showed that cells exposed to the TAW cocktail were totipotent, at all transcriptome, epigenome and metabolome levels. Hundreds of genes found in totipotent cells were switched on, while those associated with pluripotency were switched off.
To investigate how well these cells differentiated, the team cultured them in lab dishes and in live embryos in mice. In both cases, the cells behaved like totipotent stem cells – in live mice, they were able to differentiate into embryonic and extraembryonic (like the placenta) cell lineages.
This breakthrough could open up some major new opportunities, the team says. In the long run, scientists could potentially create a living organism straight from a mature cell, sidestepping the need for sperm and eggs. That could help people have children who otherwise couldn’t, or aid conservation of endangered species. The researchers do acknowledge, however, that ethical concerns will no doubt arise.
The research was published in the journal Nature.
Source: Tsinghua University
