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The Stem Cell Perfection Problem

29 August 2007 (All day)
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Andrew Paul Leonard/Photo Researchers Inc.

Quality control.
TStem cells (color enhanced) somehow keep their chromosomes in good shape.

A long-standing belief in stem cell biology is that stem cells circumvent classic cell division to keep their daughter cells healthy. But new results show that this isnt true after all; stem cells divide just like any other cell, parsing their chromosomes randomly between the progeny.

To keep organisms running smoothly, stem cells rejuvenate tissues by providing a constant supply of fresh cells. But every time a stem cell copies its chromosomes, it puts itself at risk of generating mutations in the new chromosomes. Scientists have thought for more than 30 years that stem cells avoid mutations by segregating their chromosomes asymmetrically--placing all the new chromosomes they create when replicating into the new cell and keeping the old ones as an error-free template, an idea called the "immortal strand hypothesis."

The case is not clear-cut. On the one hand, some studies have yielded evidence that backs the hypothesis. But other work in fruit flies and worms has shown that the DNA gets randomly distributed between the stem cell and its daughter cell heading for tissue. To figure out what's going on in mammalian cells, stem cell biologist Sean Morrison of the University of Michigan, Ann Arbor, and colleagues turned to blood stem cells.

First, they used a compound called BrdU to label stem cell DNA, putting it in the drinking water of adult mice for 10 days so that it slipped into the new stem cells the animals were making. Then they gave clean water to the rodents, killing some after 40, 70, and 120 days. As stem cells produced cells destined for tissue, the team reasoned, the stem cells would either keep all the BrdU, thus supporting the immortal strand hypothesis. Or, if a stem cell distributed replicated DNA randomly between itself and its daughter cell, the stem cell would run out of BrdU over time. And that was exactly what happened: By 120 days, the number of blood stem cells that held BrdU dropped to 2%. Additional experiments supported this result. "In no case did we find evidence of asymmetric chromosome segregation," says Morrison.

The experiments, reported in Nature, show that at least for blood stem cells, asymmetric segregation doesn't hold up, says developmental geneticist Allan Spradling of the Carnegie Institution in Baltimore, Maryland: "It's a fairly serious blow to those who support this as a mechanism for stem cell biology."

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