How do stem cells preserve their ability to become any type of cell in the body? And how do they “decide” to give up that magical state and start specializing? If researchers could answer these questions, our ability to harness stem cells to treat disease could explode. Now, a University of Michigan Medical School team has published a key discovery that could help that goal become reality.
In the current issue of the journal Cell Stem Cell, researcher Yali Dou, Ph.D., and her team show the crucial role of a protein called Mof in preserving the ‘stem-ness’ of stem cells, and priming them to become specialized cells in mice. Their results show that Mof plays a key role in the “epigenetics” of stem cells — that is, helping stem cells read and use their DNA. One of the key questions in stem cell research is what keeps stem cells in a kind of eternal youth, and then allows them to start “growing up” to be a specific type of tissue.
Dou, an associate professor of pathology and biological chemistry, has studied Mof for several years, puzzling over the intricacies of its role in stem cell biology. She and her team have zeroed in on the factors that add temporary tags to DNA when it’s coiled around tiny spools called histones. In order to read their DNA, cells have to unwind it a bit from those spools, allowing the gene-reading mechanisms to get access to the genetic code and transcribe it. The temporary tags added by Mof act as tiny beacons, guiding the “reader” mechanism to the right place.
“Simply put, Mof regulates the core transcription mechanism — without it you can’t be a stem cell,” says Dou. “There are many such proteins, called histone acetyltransferases, in cells — but only MOF is important in undifferentiated cells.” Via Stem cells can become anything, but not without this protein.
