In Search of a Master Controller -- MEDICA Trade Fair

In Search of a Master Controller

Photo: red blood cells

Stem cells are used to form red
blood cells; © NCI Visuals Online

An HSC is a type of adult stem cell that forms new blood cells. In a healthy human adult, HSCs are used to form about 100 billion new white and red blood cells each day.

The bioengineers Oleg Igoshin and Jatin Narula created a computer model that accurately describes the observed behavior of the three regulatory proteins that are collectively known as the Scl-Gata2-Fli1 triad. "We don't yet have the experimental verification that this is the master-level regulator for HSCs, but based on our model, we can say that it has all the properties that we would expect to find in a master-level regulator," said Igoshin.

Igoshin and Narula worked with experimentalists to create a mathematical model that accurately describes the complex interplay among the three HSC regulatory proteins in the Scl-Gata2-Fli1 triad. Based on previous studies, it was obvious that the triad plays an essential role in HSC development. In creating their computer model, the researchers were able to quantify the way the three interact and thus shed light on their combined role in regulating HSCs.

To qualify as a master regulator, the triad needed to meet two criteria. It had to act as a "bistable" switch, a one-way button that toggled from the "replenish HSC" state to the "differentiate" state. Second, it needed to ignore extraneous signals and throw the switch only when a signal persisted.

"In examining the results from the model, we found the triad did have the characteristics of a master regulator," Narula said. "The first time it's switched on, all the cells stay on. It also handles deactivation in a controlled manner, so that some cells differentiate and get deactivated and others don't. Finally, it has the ability to discern whether or not the level of signal is present only for a short burst or for a significantly long time." Igoshin said additional experimental research is needed to verify the computer model's prediction that the Scl-Gata2-Fli1 triad is the master-level controller for HSCs.; Source: Rice University