Many paths, few destinations: How stem cells decide what ...(experience inherent fluctuations in gene...)

Date:5/21/2008

experience inherent fluctuations in gene activity and protein production that can sometimes be enough to tip the balance and cause them to fall into other attractor states namely, red or white blood cell progenitors. Specific growth factors can tip the balance, but these factors are part of an overall landscape that guides cells toward different destinies. A marble going downhill will eventually end up in a valley, but which valley it falls into depends on the shape of the landscape.

Growth or differentiation factors merely increases the probability that a cell will grow or differentiate, says Donald Ingber, MD, PhD, a co-author on the paper who, with Huang, served as Changs mentor on the project. Cell differentiation is an ensemble property, a collective behavior, inherent in the systems architecture and set of regulatory interactions.

A previous study by Huang established, for the first time, that a given cell can exhibit a very different pattern of gene activity from its neighbor, taking a very different path through the landscape, yet end up in the same valley. He and his colleagues exposed precursor cells to two completely different drugs (DMSO and retinoic acid) and closely monitored the cells gene expression. Both groups of cells eventually differentiated to become neutrophils (a type of white blood cell), but the molecular paths they took and their patterns of gene expression were completely different until day seven, when they finally converged.

The landscape analogy and collective decision-making are concepts unfamiliar to biologists, who have tended to focus on single genes acting in linear pathways. This made the work initially difficult to publish, notes Huang. Its hard for biologists to move from thinking about single pathways to thinking about a landscape, which is the mathematical manifestation of the entirety of all the possible pathways, he says. A single pathway is not a good way to understand a whole process. Our goal
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Contact: Bess Andrews elizabeth.andrews@childrens.harvard.edu 617-919-3110 Children's Hospital Boston Source:Eurekalert

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