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Transparent fish provide window on blood formation and marrow transplantation

Researchers have developed powerful new techniques to see in unprecedented detail how blood-forming cells develop in zebrafish. The scientists have used this system to transplant blood cells with fluorescent "tags" so they can observe how the cells restore the blood system in mutant zebrafish that do not have any red blood cells.

The techniques may be helpful in learning how bone marrow transplants reconstitute the immune systems of patients whose immune cells have been destroyed by chemotherapy during cancer treatment.

The researchers, led by Howard Hughes Medical Institute investigator Leonard Zon, published their studies November 9, 2003, in Nature Immunology. Zon and colleagues from Children's Hospital Boston collaborated on the studies with researchers from the University of California at Los Angeles.

"The zebrafish is a fantastic organism for developmental studies because the embryos are completely transparent," said Zon. "You can watch under a microscope all the organs form within twenty-four hours in the blood system. And you can watch the heart pump blood cells through the vasculature." Furthermore, the blood-forming systems of fish and mammals still have much in common despite the fact that the two groups diverged about 450 million years ago.

Although zebrafish are excellent models for genetic studies, there have been two major obstacles that prevented researchers from using the fish to study blood formation, said Zon. Researchers had difficulty distinguishing individual cell types and they could not transplant genetically altered cells into the blood system of the zebrafish. Zon and his colleagues have now cleared both hurdles.

The researchers used flow cytometry, a technique that rapidly separates individual cells according to their optical properties. In one set of experiments, the researchers found that they could separate distinct populations of red and white bloo
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
12-Nov-2003


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