Adult Stem Cells may Have Smarts to Guard Against Cancer, Stanford Researchers Find
News Apr 20, 2007
The findings, from the lab of Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences at Stanford University School of Medicine, suggest stem cells are careful when they undergo cell division so that random mutations in their chromosomes are not passed on to the next generation of stem cells.
The results support a much-debated hypothesis proposed in 1975 by Oxford University geneticist John Cairns, PhD. Although other groups have uncovered hints that Cairns was right, Rando’s findings are the most detailed to date.
Some bewildering behavior seen in the stem cells of muscles has led researchers at the Stanford University School of Medicine to an unexpected discovery that could explain why cancer isn’t more common.
The results are published in the April 17 issue of the Public Library of Science-Biology.
Rando said no other work he’s done has created as much excitement among his colleagues in the stem cell field. “The lesson from this is that when something seems strange, don’t ignore it. Sometimes what puzzles you turns out to be the most interesting,” he said.
The idea that led to what Cairns called the “immortal strand hypothesis” was this: Stem cells found in adult tissues, such as muscles, brain or bone marrow, survive the lifetime of an animal, dividing when needed to replace cells lost to the ravages of bodily wear and tear.
Every time that cell divides, it produces one offspring that becomes the new stem cell and one shorter-lived cell that replaces the body’s tissues. In order to split one cell into two, the original must essentially photocopy its genome and then divvy up material so that each cell gets one of every chromosome. Each round of photocopying introduces new genetic errors, some of which could derail essential functions and drive the cell toward cancer.
The mystery has been that stem cells don’t morph into cancer nearly as often as one would assume, given the number of accumulating mutations.
Although some support for Cairns’ hypothesis surfaced over the years, it was never convincing enough to end the debate. Then Michael Conboy, PhD, a postdoctoral scholar in Rando’s lab, found a troubling artifact in an experiment—over, and over, and over. The only explanation for months of aggravatingly strange results was that stem cells exert some control over which chromosome copy they retain.
Rando said the next step is to figure out how the stem cells go about sorting chromosomes during cell division, determining which ones are older and thus unlikely to have mutations and which are new. For now, that’s as much of a mystery as it was when Cairns first published his hypothesis.
The spatial and temporal dynamics of proteins or organelles plays a crucial role in controlling various cellular processes and in development of diseases. However, acute control of activity at distinct locations within a cell cannot be achieved. A new chemo-optogenetic method enables tunable, reversible, and rapid control of activity at multiple subcellular compartments within a living cell.