Researchers have found that the “mother” of all stem cells, known as totipotent stem cells, have a much slower rate of DNA replication, which helps improve their efficiency at differentiating into other cells. Putting the brakes on DNA replication in lab-grown totipotent stem cells improved their efficiency, which could lead to major breakthrough for regenerative medicine.
Stem cells are famous for their ability to differentiate into various types of cells in the body, but some are more versatile than others. Multipotent stem cells reside in most tissues in the adult body, and can differentiate into a limited range of cell types. Pluripotent stem cells are a step earlier in the tree, able to split into almost any type of cell in the body. These are naturally found in developing embryos, and the state can be induced in adult cells as well, which form the majority of stem cell-based regenerative medicine.
But there’s an even earlier and more powerful type known as totipotent stem cells. These can differentiate into any type of cell in an organism, and are the only ones that can form structures like the placenta. They only appear for the first few days after fertilization, before the cells start to become more specialized.
These totipotent stem cells could be very useful for regenerative medicine, but further research is required to understand them. In the new study, researchers at Helmholtz Munich and Ludwig-Maximilians University Munich discovered a new feature of these cells that might help explain how they’re so effective.
“We found out that in totipotent cells, the mother cells of stem cells, DNA replication occurs at a different pace compared to other more differentiated cells,” said Tsunetoshi Nakatani, first author of the study. “It is much slower than in any other cell type we studied.”
DNA replication is the important process where a cell duplicates its entire genome before it divides, so that both the original and daughter cell have a copy. Totipotent stem cells may undergo this process more slowly than other cells to reduce errors, and differentiate into other cells more efficiently.
The team found that natural totipotent stem cells weren’t the only ones that underwent slower DNA replication – totipotent-like cells cultured in the lab did the same.
“This led us to the question: If we manage to change the speed at which DNA replicates, can we improve the reprogramming of cells into totipotent cells?” said Nakatani.
To test the idea, the researchers artificially slowed down DNA replication by limiting the substrate that the cells use to synthesize DNA. And sure enough, the cells that took their time replicating DNA could be reprogrammed with better efficiency.
The team says this finding could help scientists make better totipotent stem cells, improving the effectiveness of regenerative medicine. But of course, there’s still plenty of work left to be done.
The research was published in the journal Nature Genetics.
Source: Helmholtz Munich