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Self-Destructing Stem Cells Save Embryos

"Despite the huge potential of stem cells for therapeutic use, very few people have actually investigated their basic biology," said study senior researcher Mohanish Deshmukh, Ph.D., of the University of North Carolina at Chapel Hill (US). "These results could have significant implications from a therapeutic perspective."

A cell's ability to die when something goes wrong is critical. For example, a faulty self-destruct button is one factor that allows cancer cells to proliferate unchecked and cause tumors. Deshmukh and his colleagues discovered stem cells are extremely sensitive to DNA damage, which can be caused by factors such as chemicals, radiation or viruses. The experiment showed that virtually 100 percent of human embryonic stem cells treated with a DNA-damaging drug killed themselves within five hours, as compared to 24 hours for other types of cells.

The hair-trigger suicidal response is an important adaptation for embryonic stem cells, Deshmukh said, because a slower response could allow DNA damage to proliferate and harm the embryo.

The key to the stem cells' quick response is that they pre-activate a critical protein called Bax, the researchers found. In most cells, Bax is kept in an inactive form, waiting for a long chain of events to rouse it into action if the cell becomes damaged enough to kill itself. In human embryonic stem cells, the team found Bax in its active form in the Golgi apparatus, a part of the cell that processes and modifies proteins. If the cell detects DNA damage, Bax quickly moves to the mitochondrion where it signals other proteins to shut the cell down.

"What these cells do is very clever," said Deshmukh. "They have activated Bax, but they've also parked it in a safe little compartment: the Golgi."

This keeps it from accidentally triggering cell death.

This extreme sensitivity to DNA damage lasts only a few days during early development. After the embryonic stem cells begin differentiating into early progenitors that give rise to specific cell types (like heart cells or skin cells), Bax reverts to its inactive state.

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