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Why do so few stem cells convert?

Yale Medicine Magazine, 2016 - Spring

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Clues to making induced pluripotent stem cells.

Nearly a decade ago, stem cell researchers learned how to create a cell that mimics a human embryonic stem (ES) cell. Today, scientists in labs routinely create what are called induced pluripotent stem (iPS) cells by reprogramming adult somatic cells. These iPS cells are prized because, like embryonic cells, they can become almost any cell type in the body.

But in a sample of 1 million adult somatic cells, only about 100, or 0.1 percent, will convert to iPS cells in the lab—a very, very low efficiency rate, said Shanqin Guo, Ph.D., assistant professor of cell biology. Researchers don’t know why this is. “If we understand the general rules of when and how one cell type changes into another then we should in theory, be able to interconvert any other cell types,” Guo said.

Guo and her team have amassed thousands of live microscopy images of mouse adult cells turning into mouse iPS cells. They’ve tracked converted iPS cells in reverse to detect patterns that might hint at certain qualities adult cells have before they convert to iPS cells. So far, Guo has found that successfully converted iPS cells begin dividing more rapidly while they are still adult somatic cells. Now Guo wants to determine which comes first: a mechanism that turns on in somatic cells allowing them to divide more rapidly, or an inherent ability to divide rapidly that activates a certain mechanism. After that conundrum is solved, the exact molecular mechanism that aids in iPS conversion might come into focus.

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