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 specialized¹ cells in mice.

 

Their results show that Mof plays a key role in the "epigenetics（实验胚胎学）" of stem cells -- that is, helping⁴ stem cells read and use their DNA⁵. 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（错综复杂的事情） 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 spools⁶ called histones. In order to read their DNA, cells have to unwind it a bit from those spools, allowing the gene²-reading mechanisms⁸ to get access to the genetic³ code and transcribe⁹ it. The temporary tags added by Mof act as tiny beacons¹⁰, guiding the "reader" mechanism⁷ 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."

 

Dou and her team also have published on another protein involved in DNA transcription, called WDR5, that places tags that are important during transcription. But Mof appears to control the process that actually allows cells to determine which genes¹¹ it wants to read -- a crucial function for stem-ness. "Without Mof, embryonic¹³ stem cells lost their self-renewal capability¹⁴ and started to differentiate," she explains.

 

The new findings may have particular importance for work on induced pluripotent（多能的） stem cells -- the kind of stem cells that don't come from an embryo¹², but are made from "adult" tissue.

 

IPCS research holds great promise for disease treatment because it could allow a patient to be treated with stem cells made from their own tissue. But the current way of making IPSCs from tissue involves a process that uses a cancer-causing gene -- a step that might give doctors and patients pause.

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