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Colorado researcher discovers mechanism for changing adult cells into stem-like cells
Date:10/7/2010

orking on the roles of caspases in wound healing when Yaminaka published his initial iPSC work in mice. That got Li thinking about potential roles of caspases in iPSC generation.

"I thought maybe caspases could also induce iPS cells instead of the four transcriptional factors that Yamanaka used," he says. "If that was true, it would be very exciting."

For six months, his group tried different experiments using various caspase genes to coax human skin cells into iPS cells, but they had no success. Although caspases were not sufficient to make iPS cells, Li kept going with the idea that caspases were somehow involved.

They made their discovery when they introduced the caspase inhibitors into skin cells, which almost completely shut down the induction of iPS cells.

Caspases, Li says, appear to loosen up the built-in controls that make a cell differentiated or undifferentiated, just like a clutch allows a driver to switch gears while driving. Undifferentiated stem-like cells and differentiated cells from one person have the exact same genes. The difference between them is which genes are turned on or off.

In other words, he says, caspases could be the key to a kind of cellular reincarnationtaking a cell that, during human development, became a skin cell back to its original state to become any kind of cell.

"About twenty years ago, a scientist who was among the first to clone the caspase 3 gene named the gene Yama, the Hindu Lord of Death who was responsible for both killing a being and setting him on his way into his reincarnated life," Li said. "It is now becoming clear that caspases don't just kill, but they can change the cell's fate. They could be a mediator of epigenetic changes in multi-cellular organisms."


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Contact: David Kelly
david.kelly@ucdenver.edu
303-315-6374
University of Colorado Denver
Source:Eurekalert

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