Why are stem cells so willing to change?

UNC-CHAPEL HILL (US)—A protein called Tet1 appears to play a critical role in helping stem cells do what they do best: renew and become any type of cell in the body—a quality known as pluripotency.

“This may be one component of a cocktail to reprogram a specialized cell to ‘go back’ to the undifferentiated, embryonic stem cell state,” says Yi Zhang, a professor of biochemistry and biophysics at the University of North Carolina at Chapel Hill. “Then you can differentiate it into whatever cell type you want.”

Both humans and mice have Tet proteins. Observing how Tet proteins operate in colonies of mouse embryonic stem cells, Zhang’s team found that the proteins activate a gene called Nanog, which helps stem cells reproduce themselves and keep their pluripotency.

Details are reported in the journal Nature.

“There are many genes that are important for maintaining embryonic stem cells’ status,” says Zhang. “We will not understand the whole thing until we identify all the important parts of the network. From that standpoint, we have uncovered another factor in the network.”

In addition to observing cell colonies, the team examined the effects of Tet1 protein in “real life” by seeing how a mouse embryo would develop if the Tet1 protein was depleted. They found that when Tet1 is depleted in one cell of the two-cell embryo, cells derived from the Tet1 depleted cells are prone to become trophoblast cells, instead of inner cell mass, from which the pluripotent stem cells are derived.

The Tet1 protein appears to act as an enzyme to maintain the Nanog gene at an active state. When the gene is turned on, the cell maintains its identity as a stem cell.

When it’s turned off, the cell starts to lose its “stemness”.

Tet1 performs its function by regulating a modification on DNA, one kind of epigenetic modification. Effects like this are known as epigenetic changes, and they’re the reason that various types of cells in the body perform different functions even though they’re all powered by the same genetic code. It’s all about which genes are activated—and when.

“The more we understand the machinery that modifies DNA, we’ll understand more about cell fate determination,” says Zhang. Ultimately, with enough information about Tet proteins and other factors, “we will be able to use that knowledge to reprogram cells—to change their function,” he adds.

The study was supported by funding from the National Institutes of Health and the Howard Hughes Medical Institute.

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