The molecular characterization of murine hematopoietic stem cell self-renewal divisions

Every day, billions of new blood cells are produced in the human body. The origin of these cells, which are produced in the bone marrow, can be traced back to a tiny population of self-maintaining cells known as blood stem cells. Drugs used in current cancer treatments cause considerable damage to these stem cells and this can prevent more effective doses from being used for treating a number of cancers. Better ways to protect blood stem cells or to increase their numbers in a controlled fashion are needed. Additionally, many types of leukemia are known to be sustained by mutated blood stem cells. More detailed understanding of the mechanisms that regulate normal blood stem cells and how they become mutated is needed to determine how leukemia arises and how the many types of the disease can be treated more effectively. David Kent and his colleagues have recently developed a technique that allows them to isolate nearly pure populations of normal blood stem cells from the many different cell types (blood stem cells are at a frequency of between 1 in 10,000 and 1 in 15,000 cells) present in the bone marrow of adult mice. They are now able to stimulate these cells to behave differently (i.e.: to give rise to a daughter stem cell or not) in short term cell culture using different growth factors. Kent is comparing the sets of genes in these purified and differentially manipulated blood stem cell populations to identify genes that are involved in the regulation of normal blood stem cell expansion. He hopes his work will facilitate further research into the controlled expansion of stem cells and other blood cell types, and offer insight into the mechanisms by which stem cells mutate and replicate as cancer cells. He also hopes to expand fundamental knowledge of stem cells as a potential source of treatments for multiple cancers.