Over a period of five years, scientists at the Johannes Gutenberg University Mainz have managed to create a genetically modified mouse in which the activity of the blood stem cells can be tracked.
"This mouse was created from a single embryonic stem cell. We are able to observe its blood stem cells in detail and see when they divide, i.e., become active, and when they are dormant," said Dr Ernesto Bockamp of the Institute for Toxicology. Observations made by the work groups of Professor Andreas Trumpp and Dr Anne Wilson in Lausanne and Heidelberg have shown that the dormancy of certain blood stem cells can be reversed by, for example, toxic stress; they become active but return to their dormant status once their work has been completed. These findings are not only of importance for basic research, but also for applied cancer research. They were published in the latest edition of the leading scientific journal Cell .
The important task of blood stem cells is to create millions of new daughter cells in our bodies. There is also a special group of blood stem cells, however, which remains practically dormant in so-called bone marrow 'niches' in low oxygen environments. "These dormant blood stem cells divide only very rarely, which actually makes a lot of sense," explains Bockamp. "In their state of dormancy, these cells are extremely well protected against external influences such as toxic damage, but also against undesirable changes such as mutations." If the bone marrow is damaged or there is a sudden loss of many blood cells, the dormant blood stem cells are activated and turn into activated blood stem cells with the capacity for self-renewal and the production of millions of mature blood cells. Once the danger has passed and system equilibrium has been restored, these activated stem cells return to their niches and to a dormant state.
It was by creating the new mouse model that toxicologists from Mainz University established the prerequisites for obtaining these new insights. The mouse model created by Dr Leonid Eshkind made it possible to package the mouse's DNA in a luminescent green sheath. The green, fluorescent protein of a jellyfish was used to color the histones to which the DNA is attached, i.e., the normally non-luminescent packaging of the genes. "By adding a certain substance to the drinking water of the mouse, we are able to interrupt this highly specific labeling process and thus to stop the incorporation of green fluorescence into the blood stem cells," Eshkind reported. During the early 1980s, Dr Eshkind had been one of the first scientists worldwide to create genetically modified mice.