Stem Cell Circuitry
Stem Cell Circuitry
A fairly detailed press release from the Howard Hughes Medical Institute reports that researchers there have created a mathematical model of hematopoietic stem cells which helps explain how they become white blood cells. The researchers studied stem cells called myeloid progenitors, which can turn into either macrophages or neutrophil cells (vividly described as garbage disposals and vultures, respectively), and express genes for both. By looking at this “circuitry” and how the myeloid cells developed, the scientists found that increased concentration of one transcription factor normally found in macrophages turned off the signals which would direct the cell to develop into a neutrophil. Both macrophages and nuetrophils expressed low levels of this protein (PU.1); it was increasing the concentration that made a difference. They also identified a repressor gene in the neutrophil cells which shuts off the regulatory genes needed to become a macrophage.
The researchers then used the presence of the PU.1 and of the repressor gene to develop a mathematical model of the regulatory network of the stem cells. The amount of one of the two genes countering each other decreases as the other genes is increased. Theoretically this could be used to predict what a cell would become. I don’t entirely understand why having a mathematical model is more useful than looking at the genes in the standard biological ways, unless it enables more precise predictions or allows work to be done extensively on the computer before trying to duplicate the results in the lab. I would expect that there have to be certain constants for some genes and not for others, and I don’t have any guess as to whether proportionality is sustained. One of the keys seems to be that the transcription factors are operating in a binary fashion: if A is on, B must be off; if B is on, A must be off. It may be that this model provides a paradigm that can be manipulated with more control than other kinds of experiments. At any rate, it’s interesting.