In 1975, biochemist John Cairns published a phenomenal idea: that stem cells retain much of their original DNA strands despite replication. No matter how cancer or aging altered an organism, the original blueprints remained. Cairns called his idea the immortal strand hypothesis.
What's the truth behind this idea? Are stem cells really immortal?
When Cairns was formulating his hypothesis, scientists had already observed that newly formed stem cell chromosomes consisted of an older grandparent template DNA strand and a newly synthesized parent DNA strand. Of these two, the younger DNA strand was more likely to contain replication errors.
Imagine a whisper passed around a room in a parlor game, or a photocopy of a copy and you get a rough idea of what's going on. Only the accumulated changes in DNA don't merely mix up words or obscure typography. They can cause permanent mutations and ultimately lead to cancer.
Cairns theorized that when a stem cell divides, a mechanism sorts all of the chromatids (or twin halves of a replicated chromosome) containing older, more pristine grandparent templates into one daughter cell. The other daughter cell received all of the chromatids containing potentially mutated parent templates.
The inheritance was a bit lopsided, or asymmetrical.
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Testing Asymmetrical Segregation
The immortal strand hypothesis hinges on this very mechanism of asymmetrical segregation, according to Sean Morrison, director of the University of Michigan's Center for Stem Cell Biology.
"The idea only makes sense if the stem cell is dividing asymmetrically," Morrison says, "One daughter cell is a stem cell, and the other daughter cell differentiates."
In an attempt to prove or disprove the immortal strand hypothesis, various researchers set out to track stem cell replication.
"A bunch of papers have been published offering evidence in support of this immortal strand idea," Morrison says. "But the problem is that many people have not been convinced by the published evidence because in the majority of the papers that have been published, researchers have not had the benefit of rigorous stem cell markers that could really distinguish stem cells from other cells."
As a result, numerous published papers in support of immortal strand hypothesis still left some scientists skeptical. Laboratories such as Morrison's continue to test the immortal strand theory with stem cell markers.
"Our paper was the first that really did a careful job of sorting out the stem cells," Morrison says, "We looked very hard for whether we could see any evidence of asymmetric chromosome segregation either in vivo or in culture, and we absolutely couldn’t see it."
Yet even if the immortal strand hypothesis doesn't fly, Morrison says that it doesn't rule out the possibility that some varieties of stem cells are carrying out asymmetrical reproduction.
In Support of the Immortal Strand Hypothesis
Boston Biomedical Research Institutes' James Sherley, on the other hand, says that a lot of the evidence to support immortal strand hypothesis is already on the table.
"There are maybe all together now maybe 10 reports of immortal DNA strand co-segregation, three in tissues and the other ones in culture systems," Sherley says. "If you look at the reports that say to the contrary, there are only five."
Sherley believes that the problem with the dissenting papers is that they ignore cells that have properties consistent with immortal DNA asymmetric segregation.
"The reason [some researchers] ignore them is that they make a statistical error," Sherley says. "The [tests for asymmetric segregation] are fairly complicated, and the interpretation is even more complicated. One of the things that we've been trying to do is develop a simpler assay."
So Sherley hopes to develop not only another way of looking at DNA segregation, but also a method that results in fewer difficulties interpreting the data. As for continuing disagreements among researchers about the famous hypothesis, Sherley is hopeful for reconciliation.
"I think it's going to be ironed out in the next five years or so," Sherley says.
Credit: iStockphoto
Tags: DNA, Genetic Science, Stem Cells
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