The New England Patriots would never call a timeout mid-game to proclaim their status as the weaker team. Animal stem cells, however, confess their lesser rank to others all the time. In a display of altruism, they send signals to neighboring cells about their levels of stress, oxygen, or nutrition. Whatever their status, they serve a common goal‒the fitter the cell, the more competitive it is in the race to produce healthy progeny.
Ruslan M. Medzhitov, Ph.D., the David W. Wallace Professor of Immunobiology, and his lab members are studying how stem cells become winners or losers in this game of reproduction. Stem cells, they have found, appear keen to communicate a very technical aspect of their performance: their past. A stem cell’s DNA bunched inside chromosomes may look as good as new, but this doesn’t stop the cell from remembering and divulging its history. If surrounded by healthy cells, the cell with a previously repaired genome will graciously back out of the race.
When Medzhitov injected mice with stem cells that had been exposed to low-level radiation, histone proteins rushed in to “bookmark” damaged regions of DNA. DNA repair genes mended the broken letters and several days later turned themselves off. The histone proteins disappeared and the stem cell’s genome appeared perfectly normal. But a patch job is just that‒a patch job. It doesn’t guarantee against errors that might occur during the repair. This is why previously damaged stem cells declare themselves in the first place: they want to pass on only healthy cells to their offspring. (Cancer cells, which don’t play fair, never blow their cover by disclosing past damage.)
Medzhitov and his team believe that these memories of damage and repair are stored in the form of slight mutations in the telomeres, regions of repetitive DNA at the ends of chromosomes. “It’s important to understand the selection processes that go on in stem cells,” Medzhitov said. A better understanding of how everything works could affect bone marrow transplant patients, he said. This fragile patient population needs lots of healthy stem cells so that their blood-making, or hematopoietic, system has a long life and is not rife with mutations that could later lead to such health problems as cancer.