Discovery of genes that impact the development and function of blood stem cells

Researchers at the University of Minnesota have identified for the first time a group of genes that impact the development and function of blood stem cells, a discovery that brings researchers a step closer to harnessing the power of stem cells for disease treatments.

Every day, blood stem cells divide and differentiate to generate approximately 200 billion new blood cells in the bone marrow of adults. To maintain their numbers over time, blood stem cells also can divide and give rise to new blood stem cells through a process called self-renewal. What was not fully understood is which genes control the self-renewal and differentiation processes, and how these genes could be used to influence, or regulate, these processes.

The research will be published in the July issue of the journal of Public Library of Science Biology.

"If we can find a way to coax blood stem cells to self-renew and thus expand in the laboratory, doctors will have more options in treating diseases such as blood disorders, leukemias, and lymphomas," said Catherine Verfaillie, M.D., director of the University's Stem Cell Institute.

For example, researchers at the University already perform umbilical cord blood transplants to treat disease. But there are often not enough blood stem cells harvested from a single collection of umbilical cord blood to effectively treat adults and older children. This research provides insight into understanding how to stimulate blood stem cells to multiply so that scientists could generate enough cells from a single umbilical cord to treat more patients.

Importantly, the researchers developed a rapid way to identify genes that regulate the functions of stem cells that give rise to blood cells. They first developed a list of 277 genes that may regulate stem cells that make blood. They then focused on a group of 61 of these genes that had unknown roles in the function of blood stem cells.

Using zebrafish, a small fish that develops red blood cells in a way similar to humans, they "turned off" these genes in the fish embryos and watched to see if the blood formed normally. They found that disrupting the expression of 14 of these genes resulted in defects in how blood cells developed in zebrafish.

The next step is finding out how these 14 genes are involved in the development of blood cells in mammals, as well as how to harness the cells' ability to self-renew, or multiply. In the future, the techniques developed as a result of this research could be applied to other disciplines, such as neuroscience and diabetes research.

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