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Stem cells: In search of a master controller
Date:5/6/2010

terplay among the three HSC regulatory proteins in the Scl-Gata2-Fli1 triad. Based on previous studies at Cambridge, it was obvious that the triad plays an essential role in HSC development. In creating their computer model, Igoshin and Narula 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. However, he said the prediction is particularly intriguing in light of previous studies that suggest other similarly wired regulatory triads are key players in other types of stem cells, including embryonic stem cells.

"It's possible that this triad motif is reused elsewhere," Igoshin said. "The proteins could be different in each case, but the motif structure of their interconnections is common and may be repeated elsewhere in nature. That's one of the most intriguing aspects of this research."


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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

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