http://www.dailytech.com/Researchers+Find+Possible+Master+Regulator+of+Blood+Stem+Cells/article18322.htm

Scientists are racing towards a future vision in which humans can regrow failing organs and essentially obtain immortality. Along the way, they're shooting for the more obtainable aim of curing a number of diseases (cancer, Alzheimer's, Parkinson's, and paralysis, to list but a few) using stem cells.

A critical problem though is how to direct stem cells to become the proper tissue type. Within the human body, there are a rich variety of cells -- endothelial cells, muscle cells, blood cells, osteoblasts (bone), and nerve cells to name but a few. At some point in the development of the human body, these cell lines were created by a biochemical signal which instructing stem cells to become the particular cell type.

Experimentalists at Cambridge University and Rice bioengineers Oleg Igoshin and Jatin Narula have examined one of these critical biochemical signals. Based on a computer model developed at Rice and experiments at Cambridge, they believe that a trio of regulatory proteins known as the "Scl-Gata2-Fli1 triad" controls the differentiation of hematopoietic stem cells (HSCs), the self-renewing cells the body uses to make new blood cells.

In healthy adult humans, each day HSCs are responsible for the creation of 100 billion new white and red blood cells. HSCs are also capable of "self-renewing" if the bone marrow is damaged.

The research at Rice delved into looking at the three regulatory proteins and developing an mathematical model for how they interacted with HSCs. In their model, the proteins act as a bistable switch, with two states -- "replenish HSC" and "differentiate". The system ignores extraneous signals and throws the switch only when a signal persisted.

Igoshin, an assistant professor in bioengineering at Rice, comments, "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."

Jatin Narula, a Rice graduate student, adds, "In examining the results from the model, we found the triad did have the characteristics of a master regulator. 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."

Rice researchers hope that the regulatory triad motif reappears in other types of stem cells, possibly leading to more breakthroughs.

The results of the study are published in the journal PLoS Computational Biology.

May 7, 2010 (DailyTech)