Blood stem cells, which give rise to all of our blood cell types, undergo a quality assurance process after they're born. As the lab of Leonard Zon, MD, director of the Stem Cell Research program at Boston Children's, has documented, immune cells known as macrophages interact with each newly born cell. They engulf and eat any diseased or mutated stem cells, cued by a surface molecule called calreticulin, while encouraging healthy stem cells to divide and proliferate.
Now, studying zebrafish, researchers in the Zon Lab show that calreticulin—the "eat-me" signal—can be induced on blood stem cells in several ways, as can a complementary "don't-eat-me" signal the lab identified, beta-2-microglobulin (B2m). They also found ways to manipulate the two signals, potentially preventing mutant, cancerous stem-cell populations or "clones" from taking over. Their findings are published in the journal Science .
"We want to educate macrophages to take out the mutant stem cells," says Zon, who is also affiliated with the Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "They do take out the mutants periodically, but they're not efficient, and a cancer can overwhelm the system. This could be a whole new way of treating blood cancers like leukemia.
" Finding the signals of blood stem cells To better understand the eat-me signals origins, Zon and colleagues screened a panel of 1,200 chemicals in human cells. They found 93 compounds that induced production of calreticulin on t.