Not all stem cells are created equal – they are at a branching level of differentiation potential. Pluripotent stem cells are found in many tissues in adults, and they can turn into several types of cells associated with that tissue or organ that aid in healing. A step earlier in the developmental tree, pluripotent stem cells are found in embryos and can become almost any type of cell in the body.
But at the top of the chain are so-called totipotent stem cells, which can become any cell in the body, as well as supporting tissues like the placenta. These cells mark the beginning of development, including the first single cell formed from a fertilized egg, and they persist through the first few stages of development. These cells then differentiate into pluripotent stem cells and further specialize into all cells of the body as the body develops.
In recent years, scientists have been able to take adult cells and induce them to enter a pluripotent state, which forms the basis of stem cell regenerative medicine research. But in the new study, the Tsinghua University team went a step further and induced pluripotent stem cells to have totipotent properties for the first time.
The researchers set out to screen thousands of combinations of small molecules until they identified one specific combination of three that appeared to induce totipotent properties in mouse pluripotent stem cells. They named their mixture “TAW cocktail drug combination” after three of the molecules — TNPB, 1-Azakenpaullone and WS6.
Molecular testing revealed that cells exposed to the “TAW cocktail” possessed totipotent properties at all transcriptome, epigenome and metabolome levels. Hundreds of genes found in totipotent cells were turned on, while those associated with pluripotency were turned off.
To study how differentiated these cells were, the team grew the cells in lab dishes and in living mouse embryos. In both cases, the cells behaved like totipotent stem cells — in living mice, they were able to differentiate into embryonic and extraembryonic (such as placental) cell lines.
The breakthrough could open up some major new opportunities, the team said. In the long term, scientists could potentially create a living organism directly from a mature cell, bypassing the need for sperm and eggs. This could help people have children they wouldn’t otherwise have, or help protect endangered species. However, the researchers also acknowledge that ethical issues will undoubtedly arise.
The study was published innature” magazine.
